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Exopolysaccharides from Cyanobacterium aponinum from the Blue Lagoon in Iceland increase IL-10 secretion by human dendritic cells and their ability to reduce the IL-17+RORγt+/IL-10+FoxP3+ ratio in CD4+ T cells
Abstract
Regular bathing in the Blue Lagoon in Iceland has beneficial effects on psoriasis. Cyanobacterium aponinum is a dominating member of the Blue Lagoon's microbial ecosystem. The aim of the study was to determine whether exopolysaccharides (EPSs) secreted by C. aponinum (EPS-Ca) had immunomodulatory effects in vitro. Human monocyte-derived dendritic cells (DCs) were matured in the absence or presence of EPS-Ca and the effects were determined by measuring the secretion of cytokines by ELISA and the expression of surface molecules by flow cytometry. DCs matured with EPS-Ca at 100μg/ml secreted higher levels of IL-10 than untreated DCs. Subsequently, DCs matured in the presence or absence of EPS-Ca were co-cultured with allogeneic CD4(+) T cells and their effects on T cell activation analysed by measuring expression of intracellular and surface molecules and cytokine secretion. Supernatant from allogeneic T cells co-cultured with EPS-Ca-exposed DCs had raised levels of IL-10 compared with control. A reduced frequency of IL-17(+)RORγt(+) T cells was observed when co-cultured with EPS-Ca-exposed DCs and a tendency towards increased frequency of FoxP3(+)IL-10(+) T cells, resulting in a lower IL-17(+)RORγt(+)/FoxP3(+)IL-10(+) ratio. The study shows that EPSs secreted by C. aponinum stimulate DCs to produce vast amounts of the immunosuppressive cytokine IL-10. These DCs induce differentiation of allogeneic CD4(+) T cells with an increased Treg but decreased Th17 phenotype. These data suggest that EPSs from C. aponinum may play a role in the beneficial clinical effect on psoriasis following bathing in the Blue Lagoon.
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... Blue Lagoon mud is a silica-rich peloid very well-known for its microbial diversity [67][68][69][70]; filamentous bacteria that are developed in this mud have been studied to evaluate their therapeutic and dermocosmetic properties, finding that the cyanobacteria Cyanobacterium aponinum is able to secrete exopolysaccharides with anti-inflammatory properties [71,72]. ...
... Bathing in Blue Lagoon geothermal seawater has been reported to be beneficial for improving psoriasis and its anti-inflammatory properties [102,103]. The Blue Lagoon mud has been extensively investigated, both for therapeutic and cosmeceutical purposes, finding, as has been mentioned before, that exopolysaccharides could be responsible for the main properties of the peloid [71,72], but also the mineralogical compounds of the mud. Both silica mud and cyanobacterial extracts are used to prepare cosmeceutical formulations. ...
Peloids are mixtures of clays, sediments, or peat with mineral–medicinal water or seawater, or salt-lake water used in spa therapy for different treatments, including dermatological ones. The origin of peloids can be natural; that is, they are formed in situ at the place where the thermal water emerges or on the shores of the sea or salt lake, or they are prepared ad hoc from high-quality materials, such as clays or peat. Peloids are also used as cosmeceuticals in skin care to treat different skin disorders and/or conditions, such as psoriasis, eczema, and other scaly disorders, sensitive skin, and acne. This review reports all available scientific data concerning the effects and specific activities of peloids in skin care and cosmeceuticals, providing a better understanding of the clinical and cosmetic benefits. Finally, the safety and regulation of peloids are also discussed.
... In an in vitro study, Gudmundsdottir et al. [119] investigated the immunomodulatory effects of exopolysaccharides (EPSs) secreted by C. aponinum, showing that these EPSs are able to stimulate human dendritic cells (DCs) to produce vast amounts of the immunosuppressive cytokine IL-10. These DCs induced differentiation of allogeneic CD4+T cells with increased T regulatory cells but decreased Th17 phenotype. ...
... These DCs induced differentiation of allogeneic CD4+T cells with increased T regulatory cells but decreased Th17 phenotype. The authors suggested that exopolysaccharides may be involved in the therapeutic results observed in psoriasis patients following a treatment in the Blue Lagoon [119]. Later studies suggested that exopolysaccharides may induce a regulatory phenotype of DCs, T cells that are less active/inflammatory and less prone to being retained in the skin, and keratinocytes that induce less recruitment of inflammatory cells to the skin, and these effects may be mediated by the effects of EPSs on C-type lectin domain family 7 member A (CLEC7A) and Spleen tyrosine kinase (SYK), involved in inflammation, autoimmunity, and allergy [132]. ...
Over the course of the last 20 years, numerous studies have identified the benefits of thermal waters on different skin conditions. Consequently, several investigations have been carried out on their effects on the skin, which are linked to their chemical composition, and, recently, scientists have turned their attention to the role of the thermal spring’s microbiota, named “hydrobiome”, regarding these therapeutic effects. At the same time, the development of cosmetics based on pre, pro, and postbiotics has reached great relevance and research is increasing every day. This review gathers information on the biological diversity of thermal spring waters and their potential use in obtaining biological compounds, metabolites, or bacterial extracts for use in dermocosmetics as active ingredients. These bioactive compounds are able to improve dermatological diseases such as atopic dermatitis or rosacea and ameliorate pruritus and xerosis; moreover, they can increase protection against UV exposure, strengthen barrier function, maintain good homeostasis of skin defenses, repair damaged skin, promote wound healing, improve skin condition, reduce uneven skin pigmentation, and prevent skin aging. From a future perspective, fruitful cooperation among researchers, hydrologists, thermal spa centers, and cosmetic industries will drive this sector toward a better understanding of the role of the hydrobiome of thermal spring waters on healthy skin and dermatological diseases and consider the inclusion of derivatives of this hydrobiome (in the form of fermenters, lysates, extracts, etc.) in dermocosmetic formulations. Therefore, and being aware of the potential of the hydrobiome in dermatological and skin care applications, the future prospects for the use of bioactive substances derived from it in dermocosmetic formulations are promising.
... Euganean cyanobacteria have been demonstrated to produce galactolipids and exopolysaccharides with antiinflammatory and antioxidant activities. Most studies so far have focused on the isolated strains Cyanobacterium aponinum ETS-03 (Gudmundsdottir et al. 2015;Gris et al. 2017) and Phormidium ETS-05 (Bruno et al. 2005;Lenti et al. 2009;Ulivi et al. 2011;Zampieri et al. 2020). The latter is also the most abundant strain present in the mature muds (Gris et al. 2020) and it is considered the target species to certify their healing properties. ...
... It will be interesting to investigate this aspect also for the ETS-09 strain. Indeed, antioxidant and antiinflammatory activities of EPS released by bacteria and microalgae have already been reported (Raposo et al. 2015;Gugliandolo et al. 2015;Moscovici 2015), and a limited number of studies investigate these properties in cyanobacteria (Gudmundsdottir et al. 2015;Motoyama et al. 2016;Belhaj et al. 2017;Zampieri et al. 2020). The investigation of the EPS properties of the ETS-09 strain could give an important contribution to this field, also in light of the presence of a very high percentage of galacturonic acid among their monosaccharides and considering the growing body of evidence about the anti-inflammatory effects of galacturonic acid-rich polysaccharides of higher plants (Minzanova et al. 2018). ...
The therapeutic muds of the Euganean Thermal District, the oldest and largest thermal site in Europe, are recognized by the Italian Health System as an excellent treatment for osteoarticular diseases of inflammatory origin. The beneficial effects that have been demonstrated for these muds are due not only to heat and electrolytes, but also to bioactive compounds released from the microbial community, mainly composed of cyanobacteria, living in the thermal mud surface. We isolated and characterized a new coil-shaped filamentous cyanobacterium through a polyphasic approach. Molecular, morphological and biochemical data supported the description of the microorganism as a new species, Thermospirulina andreolii, of the new genus Thermospirulina, which includes other Spirulina-like cyanobacteria living in different thermal springs around the world. Biochemical analyses highlighted the capability of the strain to synthesize high amounts of phycocyanin and exopolysaccharides, with possible antioxidant and anti-inflammatory activities, suggesting its potential for contributing to the healing properties of the Euganean muds.
... Indeed, curdlan, the tolerogenic b-glucan noted above (182), is derived from the environmental bacterium Alcaligenes faecalis. In a similar manner, exopolysaccharides from Cyanobacterium aponinum, an organism represented at high levels in the waters of the Blue Lagoon of Iceland, induce human DC to express IL-10 and CD141, leading to Treg induction (190,191). Bathing in the Blue Lagoon is renowned for its abilities to alleviate psoriatic plaques (191). ...
... In a similar manner, exopolysaccharides from Cyanobacterium aponinum, an organism represented at high levels in the waters of the Blue Lagoon of Iceland, induce human DC to express IL-10 and CD141, leading to Treg induction (190,191). Bathing in the Blue Lagoon is renowned for its abilities to alleviate psoriatic plaques (191). ...
Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against environmental and self-antigens. Under some microenvironmental conditions DC develop into anti-inflammatory cells which can induce immunologic tolerance. A substantial body of literature has confirmed that in such settings regulatory DC (DCreg) induce T cell tolerance by suppression of effector T cells as well as by induction of regulatory T cells (Treg). Many in vitro studies have been undertaken with human DCreg which, as a surrogate marker of antigen-specific tolerogenic potential, only poorly activate allogeneic T cell responses. Fewer studies have addressed the abilities of, or mechanisms by which these human DCreg suppress autologous effector T cell responses and induce infectious tolerance-promoting Treg responses. Moreover, the agents and properties that render DC as tolerogenic are many and varied, as are the cells’ relative regulatory activities and mechanisms of action. Herein we review the most current human and, where gaps exist, murine DCreg literature that addresses the cellular and molecular biology of these cells. We also address the clinical relevance of human DCreg, highlighting the outcomes of pre-clinical mouse and non-human primate studies and early phase clinical trials that have been undertaken, as well as the impact of innate immune receptors and symbiotic microbial signaling on the immunobiology of DCreg.
... Also, the immunomodulatory calciferous exopolysaccharide (EPS-Ca) released from C . aponinum was benefi cial for the psoriasis patients bathing in the Blue Lagoon (Gudmundsdottir et al., 2015(Gudmundsdottir et al., , 2019. In virtue of skin conditioning functions, C . ...
... It was noteworthy that EPS-Ca secreted by C . aponinum can up-regulate the interleukin-10 (Gudmundsdottir et al., 2015) as well as inhibit the expression of spleen tyrosine kinase and the encoding gene for the Dectin-1 receptor, which showed remarkable immunomodulatory activities in vitro (Gudmundsdottir et al., 2019). In the present study, the EPS yield of Cyanobacterium sp. ...
The use of high alkaline medium is a feasible way to provide carbon source and prevent biological contamination for the outdoor cultivation of alkaliphilic microalgae and cyanobacteria. A novel cyanobacterial strain was isolated from the open pond of a marine green alga (Picochlorum sp. SCSIO-45015, Sanya, Hainan) and identified as Cyanobacterium sp. SCSIO-45682. The effects of initial sodium bicarbonate (NaHCO3) concentrations on the growth and biochemical composition of Cyanobacterium sp. SCSIO-45682 were investigated. The results demonstrated that Cyanobacterium sp. SCSIO-45682 had good adaptation to 16.8 g/L NaHCO3 (the same concentration of NaHCO3 used in Zarrouk medium for Spirulina). Moreover, the yields of biomass, polysaccharide, chlorophyll a (chl a), and phycocyanin increased under high NaHCO3 concentrations. The maximum final biomass concentration of 2.5 g/L was observed at 8.4 g/L NaHCO3, while the highest intracellular total saccharide content of 49.2% of dry weight (DW) and exopolysaccharide (EPS) concentration of 93 mg/L were achieved at the NaHCO3 concentration of 16.8 g/L. The crude protein content declined under high NaHCO3 concentrations, which provide a possible explanation for the accumulation of polysaccharide. This study shows a good potential of alkaliphilic Cyanobacterium sp. SCSIO-45682 as a polysaccharide feedstock.
... Initially, the research on cyanobacterial EPS was mainly focused on the potential of these polymers as bioremediation agents for the treatment of industrial and domestic wastewaters, namely for the removal of ammonia, phosphates, and heavy metals [17][18][19][20][46][47][48]. However, as knowledge accumulated, their putative antiviral, antimicrobial, antioxidant, anticoagulant, immunomodulatory, and antitumor activities started to be unveiled [26,29,30,[32][33][34][49][50][51][52][53][54][55][56][57][58], opening the way for the use of cyanobacterial EPS in biomedical applications. ...
... A strong correlation between the sulfate content of cyanobacterial polymers and its antioxidative and anticoagulant activities was also found [26,32,33,53], and the immunomodulatory effects of specific cyanobacterial EPS were demonstrated [54]. The presence of sulfate has also been associated to the antitumor activity displayed by some EPS [34,55], although further studies are required to unveil the exact contribution of the sulfate groups. ...
Biopolymers derived from polysaccharides are a sustainable and environmentally friendly alternative to the synthetic counterparts available in the market. Due to their distinctive properties, the cyanobacterial extracellular polymeric substances (EPS), mainly composed of heteropolysaccharides, emerge as a valid alternative to address several biotechnological and biomedical challenges. Nevertheless, biotechnological/biomedical applications based on cyanobacterial EPS have only recently started to emerge. For the successful exploitation of cyanobacterial EPS, it is important to strategically design the polymers, either by genetic engineering of the producing strains or by chemical modification of the polymers. This requires a better understanding of the EPS biosynthetic pathways and their relationship with central metabolism, as well as to exploit the available polymer functionalization chemistries. Considering all this, we provide an overview of the characteristics and biological activities of cyanobacterial EPS, discuss the challenges and opportunities to improve the amount and/or characteristics of the polymers, and report the most relevant advances on the use of cyanobacterial EPS as scaffolds, coatings, and vehicles for drug delivery.
... It became popular for people with the skin diseases, especially psoriasis, who claimed that it had significant therapeutic effects. In a study by Olafsson et al. (1994) and recently also by Gudmundsottir et al. (2015) it has been medically confirmed that regular bathing in the Blue Lagoon results in considerable improvements in healing process for these patients. The Blue Lagoon gets over 100,000 bathing visitors every year. ...
... Cyanobacteria were found to be the principal primary producers in all samples under study with Cyanobacterium aponinum as dominating member of the Blue Lagoon's microbial ecosystem. C. aponinum is biotechnologically very interesting species, the EPS component of which may play a role in the beneficial effect in psoriasis following bathing in the Blue Lagoon (Gudmundsottir et al., 2015). ...
The Blue Lagoon is a shallow geothermal lake which contains sea- and freshwater and is extremely high in silica content. This study has provided the first in-depth molecular survey of its planktic microbial inhabitants and laid the groundwork for future environmental and physiological work. Most MiSeq sequences obtained were affiliated with Alphaproteobacteria (36%), Cyanobacteria (26%), and Gammaproteobacteria (24%). Cyanobacteria were found to be the principal primary producers with 99.8% of the cyanobacterial sequences belonging to the unicellular Cyanobacterium aponinum. Filamentous genera: Halomicronema and Phormidium were very minor and present only outside the bathing area. The calculated diversity was typical of samples from extreme environments. Elevated salinity and high concentration of silicium attract extremophiles that are either highly adapted specialists for certain conditions or generalists with wide tolerance ranges. Relatively few abundant phyla were represented; 95% of observed OTUs consisted of less than ten sequences and only 0.5% had more than 1000 sequences. All rarefaction curves were far from saturation and a higher number of sequences is apparently required to cover the whole community diversity. Although, the diversity of the abundant taxa was limited, the rare biosphere, detectable only with next generation sequencing, increased significantly the diversity.
... Other C. aponinum strains were later found in the Oman desert (Winckelmann et al. 2015) and in the Blue Lagoon, Iceland, thermal springs (Petusdottir et al. 2009). The latter was also recently demonstrated to be able to produce RPS with immunomodulating and anti-inflammatory effects, potentially beneficial for patients affected by psoriasis (Gudmundsdottir et al. 2015). In addition, this species was recently admitted in the international cosmetic ingredient list thanks to skin conditioning properties. ...
... Released exopolysaccharide production (RPS) in the growth medium was evaluated in the supernatant obtained after removing cells by centrifugation at 1700×g for 30 min at 4°C. The supernatant was then dialyzed against a minimum of 10 volumes of distilled water for 72 h, in continuous stirring at 4°C, cutting off polysaccharides with a molecular weight over 3.500 Da in order to avoid a possible influence of monosaccharides and oligosaccharides in RPS content determination (Spectra/Por dialysis membrane with 3500 Da cutoff, Spectrum Laboratories, USA) (Mota et al. 2013;Gudmundsdottir et al. 2015). RPS concentrations of samples were then determined according to the Dubois method (DuBois et al. 1956), using D-glucose as standard. ...
Cyanobacterium aponinum is a thermotolerant cyanobacterium species isolated from different thermal springs and showing potential therapeutic application thanks to the synthesis and release of exopolysaccharides with anti-inflammatory and immunomodulating properties. This work investigates the effects of temperature and light on growth rate, biomass yield, and released polysaccharides (RPS) synthesis in C. aponinum cultures. The highest biomass productivity was obtained at 40 °C (about 92 mg L⁻¹ d⁻¹), while the highest RPS synthesis rate (about 10 mg L⁻¹ d⁻¹) was detected at 35 °C. At this temperature, the influence of light intensities, between 15 and 650 μmol photons m⁻² s⁻¹, was also evaluated. C. aponinum showed the highest productivity in biomass (about 280 mg L⁻¹ d⁻¹) and RPS (about 20 mg L⁻¹ d⁻¹) at 500 μmol photons m⁻² s⁻¹. Interestingly, this strain also had the ability to accumulate other high-value compounds such as phycocyanin, zeaxanthin, and β-carotene suggesting that C. aponinum can be used for the industrial production of multiple molecules of biotechnological interest.
... Some of these organisms were found to be more abundant in mud biofilms at temperatures lower than 45°C (Phormidium sp. ETS-05, Cyanobacterium aponinum ETS-03) have been already taxonomically characterized (Ceschi Berrini et al., 2004;Moro et al., 2007) and investigated for the production of different compounds of interest that act as antiinflammatory, antioxidant, and immune modulating agents (Ulivi et al., 2011;Gudmundsdottir et al., 2015;Zampieri et al., 2020Zampieri et al., , 2022Zampieri et al., , 2023. Instead, except for Thermospirulina andreolii ETS-09 (Moro et al., 2021), little information is available on species that thrive at higher temperatures arranged in dense and thick microbial mats, enriched in filamentous species (Gris et al., 2020). ...
Hot springs are considered modern terrestrial environments analogous to Archean continental surfaces, where photosynthetic life could have evolved. In this habitat cyanobacteria dominate thanks to the adaptations to high temperature and the capability to acclimate to low light intensity and far-red enriched spectra typical of microbial biofilms. The isolation and characterization of new cyanobacterial species from these environments is fundamental to discover genetic and physiological traits allowing them to thrive under such unfavorable conditions, giving useful information to understand the evolution and plasticity of oxygenic photosynthesis as well as to assess their metabolic biodiversity for biotechnological purposes. In this study, we present the polyphasic characterization of a filamentous cyanobacterium, denominated strain ETS-13, isolated from mud biofilms collected in the Euganean Thermal District (Italy). The area is known since ancient times for the presence of thermal springs and muds exploited for the beneficial properties linked to heat, electrolytes, and organic compounds produced by the microbiota. The ETS-13 genome was assembled and annotated, while phylogenetic analyzes were performed using a combined approach based on the 16S rRNA sequence and considering the 16S-23S ITS secondary structures. In addition, morphological, biochemical, and physiological features of the organism were investigated, allowing its classification as a new species of the Kovacikia genus, named Kovacikia euganea, which formed a cluster with other species of Leptolyngbyaceae from thermal environments. Interestingly, the strain was the first isolated in Italy capable of performing Far-Red Light Photoacclimation (FaRLiP) when exposed to far-red light, a feature found in other species of the same genus so far tested for this acclimation and isolated form geographically distant and different environments.
... C. aponinum also demonstrates great potential for the accumulation of versatile high-value compounds, e.g., exopolysaccharides [42], C-phycocyanin [40,43,44], zeaxanthin, β-carotene [42] as well as lipids [45], glycogen and protein [46]. The extracellular polysaccharides secreted from C. aponinum displayed significant immunomodulatory and anti-inflammatory effects, potentially beneficial for the treatments of psoriasis [47,48]. Due to its significant skincare properties, fermented products of C. aponinum have been included in the International Nomenclature of Cosmetic Ingredients list [49]. ...
Polysaccharides from cyanobacteria are extensively reported for their complex structures, good biocompatibility, and diverse bioactivities, but only a few cyanobacterial species have been exploited for the biotechnological production of polysaccharides. According to our previous study, the newly isolated marine cyanobacterium Cyanobacterium aponinum SCSIO-45682 was a good candidate for polysaccharide production. This work provided a systematic study of the extraction optimization, isolation, structural characterization, and bioactivity evaluation of polysaccharides from C. aponinum SCSIO-45682. Results showed that the crude polysaccharide yield of C. aponinum reached 17.02% by hot water extraction. The crude polysaccharides showed a porous and fibrous structure, as well as good moisture absorption and retention capacities comparable to that of sodium alginate. A homogeneous polysaccharide (Cyanobacterium aponinum polysaccharide, CAP) was obtained after cellulose DEAE-52 column and Sephadex G-100 column purification. CAP possessed a high molecular weight of 4596.64 kDa. It was mainly composed of fucose, galactose, and galacturonic acid, with a molar ratio of 15.27:11.39:8.64. The uronic acid content and sulfate content of CAP was 12.96% and 18.06%, respectively. Furthermore, CAP showed an in vitro growth inhibition effect on human hepatocellular carcinoma (HepG2) cells. The above results indicated the potential of polysaccharides from the marine cyanobacterium C. aponinum SCSIO-45682 as a moisturizer and anticancer addictive applied in cosmetical and pharmaceutical industries.
... Moreover, temperature is a key parameter that has a strong influence on microalgae metabolism; indeed, high temperature can enhance EPS production [94]. Recently, Gudmundsdottir and colleagues investigated the anti-inflammatory role of EPSs produced by Cyanobacterium aponinum [69], a thermophilic cyanobacterium grown at 40 • C [95]. The research was mainly devoted to elucidating the molecular mechanism that underlies psoriasis, using dendritic cells, keratinocytes, and T cells as experimental systems. ...
Extremophilic microorganisms play a key role in understanding how life on Earth originated and evolved over centuries. Their ability to thrive in harsh environments relies on a plethora of mechanisms developed to survive at extreme temperatures, pressures, salinity, and pH values. From a biotechnological point of view, thermophiles are considered a robust tool for synthetic biology as well as a reliable starting material for the development of sustainable bioprocesses. This review discusses the current progress in the biomanufacturing of high-added bioproducts from thermophilic microorganisms and their industrial applications.
... EPS-Ca. EPS-Ca also demonstrated to reduce keratinocyte secretion of chemokines CCL20 and CXCL10 that are involved in the recruitment of inflammatory cells [57]. In this scenario, this investigation delved into the microbiological profile of LS-TSW. ...
The development of cosmetic ingredients improving the management of skin with irritation proclivity is an actual need. However, medical recommendations in specific cases, such as sensitive skin, include the use of as few and low-reactive ingredients as possible. In this context, we here describe the development of a new ingredient consisting of a mixture of thermal water and a diatom algae extract. First, we characterized a thermal spring water (La Solia, LS-TSW). Attending to its chemical composition, LS-TSW displayed an exclusive combination of different inorganic elements, with interesting potential properties when compared with other commercial spring waters. Then, LS-TSW hydrobiome was studied, and after finding specimens of Phaeodactylum-like sp., we proposed potentiating LS-TSW benefits with its combination with an oil extract of Phaeodactylum tricornutum (PtOE). Finally, we assessed the potential of the mixture during pro-inflammatory stimulation, in the first instance using an immune cell model, and then in an in vitro system mimicking keratinocytes under skin irritation. In the last-mentioned model, the ingredient of interest effectively attenuated the induced levels of different pro-inflammatory mediators (IL-6, IL-1, TNFα, NF-κB, and CCL1), at the level of gene expression. Thus, our results highlight the potential benefits of this combination in the context of skin irritation, opening roads for its use in new skincare regimens, and addressing an important dermatological concern.
... play vital role as they help to increase the immune response, enhance antitumor activity, and promote growth of animals Kang et al. 2013). In vitro effects of immunomodulation by exopolysaccharides have been reported for Cyanobacterium aponinum (Gudmundsdottir et al. 2015). In pharmaceutical industry, some of these cyanobacterial EPS like pullulan and dextran have gained remarkable importance (Singh et al. 2019). ...
Exopolysaccharide (EPS) extraction from cyanobacteria is an effective biotechnological approach with imperious applications in different industries. Cyanobacteria being photoautotrophic organisms show diverse cellular arrangements under stressful environmental conditions like exposure to desiccation, ultraviolent radiation, and high temperature or pressure. These cyanobacteria, because of their environment-friendly nature and fast growth, are considered as a renewable source to produce exopolysaccharides with applications in pharmaceutical, food, and cosmetics production, treatment of wastewater, heavy metal removal, and many more. Most of the research is conducted on the extraction of exopolysaccharides, like the use of conventional alcoholic precipitation, tangential filtration, and certain other alternative methods in addition to the bioprocessing of exopolysaccharides from cyanobacteria. Currently, scientists are working on the manipulation of cyanobacterial exopolysaccharides by developing cultures and processes, so that better production of exopolysaccharides can be attained. This chapter highlights the structural and physicochemical characterization of the EPS. Furthermore, it highlights the protocols for the enhancement, processing, and extraction of EPS along with the potential applications of cyano-EPS in different fields of bio-industry.
... Spirulan is also used as a gluing agent that assists in the closure of soft tissues after surgery (Witvrouw et al., 2005). Cyanobacterium aponinum PCC10605 produced EPS-Ca is used in immunomodulatory effects under in vitro conditions (Gudmundsdottir et al., 2015). Precipitation, complexation, solvent extraction, coagulation, and ion exchange processes are used to eradicate heavy metals from water; each of these methods has advantages and disadvantages due to their high cost and ineffective removal of heavy metals when these contaminants are present in trace amounts (De Philippis et al., 2011). ...
... Gudmundsdottir et al. [24] conducted two in vitro studies to assess the effects of the exopolysaccharides (EPSs) secreted by Cyanobacterium aponinum (EPS-Ca), a prevalent organism in the Blue Lagoon. In the first study, they maturated human monocyte-derived dendritic cells in the absence or presence of EPS-Ca and measured the secretion of cytokines by ELISA and the expression of surface molecules by flow cytometry. ...
Background: Thermal waters have been showing different beneficial effects on the skin due to their physicochemical composition. The beneficial effect of thermal water in the treatment of some skin diseases may thus justify its use as an active ingredient in cosmetic formulations. The main objective of this work was to demonstrate the potential of incorporating thermal water as an active ingredient in cosmetic formulations. (2) Methods: A descriptive literature review was carried out by the analysis of scientific articles in PubMed and Google Scholar databases. Twelve thermal spring waters were found (Avène, Blue Lagoon, Comano, Cró, Dead Sea, La Roche-Posay, Monfortinho, Saint-Gervais, Salies-de-Béarn, São Pedro do Sul, Uriage and Vichy) with potential as an active in cosmetic products, demonstrated through in vitro studies evaluating the different activities/properties and clinical trials in healthy volunteers or with skin pathologies. (3) Results: For these studies, in natura thermal water as well as incorporated in cosmetic formulations were used. In in vitro studies, most thermal waters have been shown to have activities on membrane fluidity, skin barrier repair, antiradical, antioxidant, anti-inflammatory and immunomodulatory properties, proliferative activity, regulation of processes involved in ageing and moisturizing properties. In clinical trials, cosmetic thermal waters reduced skin discomfort through their soothing and exhibited moisturizing and anti-irritant properties. (4) Conclusions: The effect of thermal waters on the skin and the absence of side effects reported in different studies allows them to be used as an adjuvant or in the treatment of various skin disorders and may play an important role in the cosmetics industry. However, further clinical trials are needed to assess their effectiveness and safety.
... Los exopolisacáridos cianobacterianos han demostrado tener propiedades regeneradoras de tejidos, como agentes de proliferación celular en la reparación de heridas (Gudmundsdottir et al. 2015;Fukushima et al. 2016), y los conocimientos actuales sobre la variedad y los propiedades funcionales de los exopolisacáridos cianobacterianos permiten desarrollar avances tecnológicos en la medicina regenerativa. ...
The cyanobacteria is a photosynthetic microorganism group that show up on earth around 2,4 billion years. They are prokaryotic organisms located by its characteristics in the group of Gram-negative bacteria. The cyanobacteria show complex metabolic ways for the carbohydrates synthesis; that allowed them to synthetize intracellular carbohydrates, polymer reserves like glucan and extracellular polysaccharides structurally complex. The extracellular polysaccharides are presented associated with the cellular surface form of envelops, capsules and viscous material and the polysaccharides released into the environment. The dissolved exopolysaccharides are soluble portions of polysaccharide material released into the environment throughout the external envelops or byproduct by complex biosynthetic processes. The importance of this polymers lies in the ease of recovery of the culture medium and due to their complex structure includes sulfate, phosphate, acetate groups, uronic acids, protein fractions and also a complex structure and monosaccharide composition, which gives them interesting physicochemical properties for various fields such as: biomedicine, pharmaceutics, food industry, remediation of residual effluents, etc. The use of cyanobacteria in wastewater treatment has been widely documented in the pig slurry purification with interesting results shown. However, is indispensable, to evaluate the remediation potential of these microorganisms in other types of industrial effluents.
... The immunomodulation effect of sulphated EPSs produced by Cyanothece sp. PE 14 [149] or by Cyanobacterium aponinum [150] was also demonstrated in animal and human cell lines. N. commune extract resulted in being effective in downregulating IL-6 [151] and is, therefore, potentially useful for anti-allergic and wound-healing therapeutic purposes [152]. ...
Simple Summary
Microalgae-based biorefineries allow the simultaneous production of microalgae biomass enriched in a particular macromolecule and high-added and low-value products if a proper selection of the microalgae species and the cultivation conditions are adequate for the purpose. This review discusses the challenges and future trends related to microalgae-based biorefineries stressing the multi-product approach and the use of raw wastewater or pretreated wastewater to improve the cost-benefit ratio of biomass and products. Emphasis is given to the production of biomass enriched in carbohydrates. Microalgae-bioactive compounds as potential therapeutical and health promoters are also discussed. Future and novel trends following the circular economy strategy are also discussed.
Abstract
Microalgae have demonstrated a large potential in biotechnology as a source of various macromolecules (proteins, carbohydrates, and lipids) and high-added value products (pigments, poly-unsaturated fatty acids, peptides, exo-polysaccharides, etc.). The production of biomass at a large scale becomes more economically feasible when it is part of a biorefinery designed within the circular economy concept. Thus, the aim of this critical review is to highlight and discuss challenges and future trends related to the multi-product microalgae-based biorefineries, including both phototrophic and mixotrophic cultures treating wastewater and the recovery of biomass as a source of valuable macromolecules and high-added and low-value products (biofertilizers and biostimulants). The therapeutic properties of some microalgae-bioactive compounds are also discussed. Novel trends such as the screening of species for antimicrobial compounds, the production of bioplastics using wastewater, the circular economy strategy, and the need for more Life Cycle Assessment studies (LCA) are suggested as some of the future research lines.
... Mud maturation experiments carried out comparing the natural substrate with commercial ones (such as bentonite) showed in fact a strong impairment of the green biofilm growth in the second case [14]. Moreover, surveys on some of the Cyanobacterial species colonizing the Euganean muds also demonstrated their ability to produce bioactive molecules with anti-inflammatory and antioxidant properties [15][16][17], tested both in vitro [18][19][20] and in vivo [21,22]. The isolated Phormidium sp. ...
The Euganean Thermal District has been known since Roman times for the therapeutic properties of peloids, obtained from natural clays that have undergone a traditional maturation process. This leads to the growth of a green microbial biofilm with Cyanobacteria and the target species Phormidium sp. ETS-05 as fundamental components for their ability to synthetize anti-inflammatory molecules. Currently, in-depth studies on the microbiota colonizing Euganean peloids, as in general on peloids utilized worldwide, are missing. This is the first characterization of the microbial community of Euganean thermal muds, also investigating the effects of environmental factors on its composition. We analysed 53 muds from 29 sites (Spas) using a polyphasic approach, finding a stable microbiota peculiar to the area. Differences among mud samples mainly depended on two parameters: water temperature and shading of mud maturation plants. In the range 37–47 °C and in the case of irradiance attenuation due to the presence of protective roofs, a statistically significant higher mud Chl a content was detected. Moreover, in these conditions, a characteristic microbial and Cyanobacteria population composition dominated by Phormidium sp. ETS-05 was observed. We also obtained the complete genome sequence of this target species using a mixed sequencing approach based on Illumina and Nanopore sequencing.
... µm long. In spite of several reports of isolated strains in databases, there is not sufficient morphological and genetic information about this genus and few strains of Cyanobacterium sp. have been collected in thermal and freshwater environments (Moro et al. 2007, Gudmundsdottir et al. 2015, Winckelmann et al. 2015. Xenococcus genus (Bornet and Thuret 1880) comprised 30 taxonomically accepted species. ...
Central America is one of the most important biodiversity hotspots in the world, and Costa Rican microbial communities from thermal springs are the best characterized in the isthmus. Miravalles is an inactive quaternary stratovolcano, and the Rincón de la Vieja is a unique active volcano, in whose slopes diverse hydrothermal springs such as Las Lilas are located. These springs harbor extensive microbial mats, whose diversity has been studied. Based on their importance as primary producers, in this study we focused on cultured cyanobacterial diversity from two geothermal environments of northern Costa Rica. Several culture, molecular, and taxonomic techniques were employed to maximize the results of a polyphasic approach. Sample collection sites were physicochemically described, and strains were isolated and characterized by light microscopy and electron microscopy. Phylogenetic analysis was performed using 16S rRNA gene sequences and amplified ribosomal DNA restriction analysis (ARDRA). Fifty six phylotypes were isolated and classified in 21 morphotypes and identified into 14 genera, some of them might be new species within these genera. Furthermore, according to phylogenetic analysis, there are three possible new genera in our collection. Miravalles and Las Lilas thermal springs are reservoirs of novel phylogeographic lineages of phototrophic microorganisms. This study is the first report of strains that belong to the genera Gloeocapsa, Stanieria, Microseira, Klisinema and Oculatella isolated from thermal springs and growing at temperatures above 50°C. We also obtained isolates assigned to Synechococcus, Leptolyngbya spp., and Fischerella, which are considered typical strains in these environments.
... Physico-chemical properties of cyanobacterial EPS have shown promising performances suitable for the industry as gums, bioflocculants, soil conditioners, biolubrificants, and biosorbents [11][12][13]. The presence of non-carbohydrate substituents is proven to act as biological weapons, showing anti-viral, anti-microbial, anti-tumoral activity [14][15][16][17]. Their potential has been already explored as drug delivery technology [18,19]. ...
Cyanobacteria have the potential to become an industrially sustainable source of functional biopolymers. Their exopolysaccharides (EPS) harbor chemical complexity, which predicts bioactive potential. Although some are reported to excrete conspicuous amounts of polysaccharides, others are still to be discovered. The production of this strain-specific trait can promote carbon neutrality while its intrinsic location can potentially reduce downstream processing costs. To develop an EPS cyanobacterial bioprocess (Cyano-EPS) three steps were explored: the selection of the cyanobacterial host; optimization of production parameters; downstream processing. Studying the production parameters allow us to understand and optimize their response in terms of growth and EPS production though many times it was found divergent. Although the extraction of EPS can be achieved with a certain degree of simplicity, the purification and isolation steps demand experience. In this review, we gathered relevant research on EPS with a focus on bioprocess development. Challenges and strategies to overcome possible drawbacks are highlighted.
... Phycocyanin is utilized as a natural colorant and as a supplement in food, drink, and cosmetics (Setyoningrum Tut i k a n d Nu r 201 5). It is recently found that exopolysaccharides secreted by Cyanobacterium aponinum have immunomodulatory effects (Gudmundsdottir et al. 2015). Presently, Arthrospira is used in many industrial Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10811-019-01851-4) ...
Cyanobacteria have tremendous potential to produce bioactive molecules, which makes them a highly lucrative organism for use in industrial applications. In the present study, the first commercial nutrient medium for Cyanobacterium aponinum is developed and a process for large scale cultivation of cyanobacteria is established by combining economical medium, pre-emptive nutrient feeding strategy, and semi-continuous mode (SCM) of cultivation. The parameters measured were growth in terms of OD750 biomass, total nitrogen, nitrate, and phosphorous. Results indicated 13% more biomass yield in urea-phosphoric acid medium (UPA), in comparison to blue-green medium (BG-11). Biomass concentration was 5.3 and 4.7 g L⁻¹ with UPA and BG-11 media, respectively. Urea was found to be a preferred nitrogen source for C. aponinum. Nutrient-dosing studies with UPA medium in SCM of operation resulted in an average daily biomass productivity of ~ 0.44 g L⁻¹ day⁻¹, which is significantly higher than those reported in previous studies. Here, the stoichiometric requirement of nitrogen and phosphorous was found to be 31 mg L⁻¹ and 4.5 mg L⁻¹, respectively. Stoichiometric nutrient addition in SCM resulted in a reduction in nutrient loss in blow down. In addition, the outdoor scale-up studies in flat panel photobioreactors further established the efficacy of UPA medium. Cost analysis of media revealed that UPA medium is 4.4 times less expensive than BG-11 and hence is a suitable and economical medium for large scale cultivation of C. aponinum. Further, this nutrient feeding strategy has wider applications which can be extended to other algal strains and cultivation systems.
... algae and plants), decreasing the polymer production costs. Therefore, the industrial interest on cyanobacterial extracellular carbohydrate polymers has been rising, namely for biomedical and pharmaceutical applications, due to their antiviral [4], antioxidant [5] or immunomodulatory [6] activities. ...
Cyanobacterial extracellular carbohydrate polymers are particularly attractive for biotechnological applications.
Previously, we determined the monosaccharidic composition of the polymer of a Synechocystis ΔsigF
overproducing mutant. Here, we further characterized this polymer, demonstrated that it is possible to recover
it in high yields, and successfully use it for biomedical research. This amorphous polymer is formed by a mesh
of fibrils/lamellar structureswith high porosity, is constituted by highmolecularmass fractions, is highly sulfated
and displays low viscosity, even in highly concentrated aqueous solutions. FTIR analysis confirmed the presence
of several functional groups. We demonstrated that the ΔsigF polymer has strong biological activity, decreasing
the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53
and caspase-3 activation. Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable
production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical
applications.
... In a study published in 2015, the authors found that exopolysaccharides (EPSs) secreted by C. aponinum determines the maturation of dendritic cells, increased the levels of IL-10 and the frequency of FoxP3(+)IL-10(+) T cells and decreased the IL-17(+)RORγt(+)/FoxP3(+)IL-10(+) ratio. The authors therefore concluded that bathing in the Blue Lagoon could be advantageous for psoriatic patients [94]. All this data supports the role of IL-10 in the pathogenesis of psoriasis and supports the idea that targeting IL-10 might be useful in psoriasis. ...
Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-β1 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris.
... (Ma & Gao, 2009). Mat formation (Rastogi et al., 2014c;Häder & Gao, 2015) or synthesis of extracellular polysaccharides (EPS) are other mechanisms to reduce the exposure to excessive radiation (Gudmundsdottir et al., 2015). Solar UV-B can exert its detrimental action either directly by attacking vital biomolecules or by the formation of reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) or hydrogen peroxide (Rastogi et al., 2014a). ...
Phytoplankton produce about 50% of the global biomass and take up an equal amount of CO2 from the atmosphere as all terrestrial ecosystems taken together. Productivity of phytoplankton depends on a number of environmental factors many of which are altering with climate change. Higher temperatures augment productivity in colder climates, but shift habitats towards the poles and changes species composition. Increase in temperature also increases stratification and thus exposes organisms in the photic zone to higher solar visible and UV radiation. It also limits the penetration of nutrients from the water column below. Climate change alters precipitation patterns, water currents and wind effects increasing concentrations which decrease the penetration of solar radiation in coastal areas, but can extend hundreds of km into the open sea with the plumes of large rivers. Increasing pollution from terrestrial runoff and maritime sources affects productivity and species composition.
... It has recently been suggested that the use of natural antioxidants, such as vitamins A and E, in skin care formulations could provide a preventive therapy for skin photoaging [8,9]. Moreover, beauty-improving formulations of skin care emulsion with seaweed extracts or micro algae added have also been reported [10]. ...
A water and an acetone extract of the Icelandic brown algae Fucus vesiculosus were evaluated as potential natural sources of antioxidant compounds in skin care emulsions. To assess their efficacy in inhibiting lipid oxidation caused by photo‐ or thermoxidation, they were stored in darkness and room temperature as control conditions, and compared to samples stored under accelerated conditions (light and room temperature, or darkness and 40°C). The presence of extracts in the skin care emulsions induced remarkable colour changes when the emulsions were exposed to light, and more extensively under high temperature. High temperature also caused greater increments in the droplet size of the emulsions. The analysis of the tocopherol content, peroxide value and volatile compounds during the storage revealed that, whereas both water and acetone extracts showed (at 2 mg/g of emulsion) protective effect against thermooxidation, only the water extract showed antioxidant activity against photooxidation.
Practical applications: This research is the basis of developing natural antioxidants derived from seaweed to limit lipid oxidation in skin care products.
Skin care emulsions are exposed to light (A+) or elevated storage temperatures (H0) to promote lipid oxidation during storage. Control samples are stored at ambient temperatures in the dark (A0). Two Icelandic brown alga Fucus vesiculosus extracts, water (WE) and acetone (AE) extract, were added as natural antioxidants to control lipid oxidation and ensure a stable product. Both extract (depending on concentration, 1 or 2) decreased photooxidation of skin care emulsions compared to the reference (REF) without added extract, as decreased formation of secondary volatile oxidation products was observed. However, the presence of extracts in the skin care emulsions induced remarkable colour changes during storage. Moreover, samples exposed to elevated storage temperatures increased oil droplet size and resulted in disrupted emulsion structure (syneresis) by day 35.
The numerous forms of extracellular polymeric substances (EPS) produced by soil algae, as well as their applications, are covered in different sections in this chapter. Algal biomass is mostly used to isolate EPS such as ulvans, carrageenan, alginates, proteins, and lipids. The commercial highlights of EPS are examined in detail in a separate section. In the last section of the chapter, frequent applications of EPS in bioremediation for wastewater treatment, i.e., removal of emerging toxins, at the laboratory scale, pilot scale, and industrial level are highlighted.
b>Introduction: Bathing in the Blue Lagoon (BL) in Iceland benefits patients with psoriasis. Accordingly, the BL water contains algae with biological activities that improve skin barrier function and affect T-cell responses relevant for psoriasis. Bathing in the BL is also becoming increasingly popular among healthy individuals and anecdotal evidence suggests positive effects on uneven skin pigmentation. Objective: The aim of the study was to address the impact of BL algae on skin pigmentation. Methods: In this work, in vitro gene expression studies in melanocytes and a noninvasive in vivo study were conducted. Results: We here report that normal human epidermal melanocytes, which had been treated with nontoxic concentrations of BL algae, show a significantly reduced expression of α melanocyte-stimulating hormone-induced expression of genes important for melanin synthesis, such as tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, melan A protein, and pre-melanosome protein. This in vitro observation prompted us to conduct a randomized, double-blind, intra-individual, comparative split-face in vivo study, in which 60 volunteers with pre-existing facial pigment spots were treated twice daily with a BL algae containing serum or a vehicle control. We found that constitutive skin pigmentation as determined by colorimetry (individual typology angle and luminescence) did not differ significantly between vehicle- and serum-treated skin sites. In marked contrast, digital photography under cross-polarized lighting and RBX technology (VISIA CR) revealed that the number of pigment spots in the serum-treated face decreased significantly compared to the vehicle-treated side. Conclusion: Thus, BL algae can affect human melanocyte function in vitro and reduce uneven facial skin pigmentation in vivo.
Psoriasis is a non-communicable, heterogeneous, autoimmune, inflammatory skin disease characterised by reddish, scaly plaques that grow over time. Psoriasis affects people in all countries with all age groups. The World Psoriasis Day organisation claims that out of 125 million people on this planet - Psoriasis affects about 2.5% to 3% of the population. The symptoms of psoriasis are unpredictable, and there are several external factors and associated comorbidities including psoriatic arthritis, renal failure, gastrointestinal disease, cardiovascular disease, stroke, obesity, diabetes, hypertension, mental disorders, cancer and a higher risk of death due to the systemic inflammation associated with the condition. In 2014, the WHA resolution identified that psoriasis is a severe non-communicable condition that affects both men and women. According to the declaration, several individuals suffer excessively from psoriasis all across the world as a result of inaccurate or delayed diagnosis, poor treatment solutions, minimal healthcare access, and social stigmatisation. Focusing on the function of cytokines and small-molecule inhibitors in the pathogenesis of disease could benefit the development of newer anti-psoriasis therapies. This is an updated comprehensive review that provides insight into the management of psoriasis with different therapeutic approaches and gives a brief idea about immunological signalling molecules that play a crucial part in the disease progression. We also highlighted the potential involvement of interleukins in the context of psoriasis, which may help the research community in its hunt for new treatments.
Introduction:
Bathing in the Blue Lagoon (BL) in Iceland benefits patients with psoriasis. Accordingly, the BL water contains algae with biological activities that improve skin barrier function and affect T-cell responses relevant for psoriasis. Bathing in the BL is also becoming increasingly popular among healthy individuals and anecdotal evidence suggests positive effects on uneven skin pigmentation.
Objective:
The aim of the study was to address the impact of BL algae on skin pigmentation.
Methods:
In this work, in vitro gene expression studies in melanocytes and a noninvasive in vivo study were conducted.
Results:
We here report that normal human epidermal melanocytes, which had been treated with nontoxic concentrations of BL algae, show a significantly reduced expression of α melanocyte-stimulating hormone-induced expression of genes important for melanin synthesis, such as tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, melan A protein, and pre-melanosome protein. This in vitro observation prompted us to conduct a randomized, double-blind, intra-individual, comparative split-face in vivo study, in which 60 volunteers with pre-existing facial pigment spots were treated twice daily with a BL algae containing serum or a vehicle control. We found that constitutive skin pigmentation as determined by colorimetry (individual typology angle and luminescence) did not differ significantly between vehicle- and serum-treated skin sites. In marked contrast, digital photography under cross-polarized lighting and RBX technology (VISIA CR) revealed that the number of pigment spots in the serum-treated face decreased significantly compared to the vehicle-treated side.
Conclusion:
Thus, BL algae can affect human melanocyte function in vitro and reduce uneven facial skin pigmentation in vivo.
The cyanobacterial exopolysaccharides (EPSs) are considered as one of the important group of biopolymers having significant ecological, industrial, and biotechnological importance. Cyanobacteria are regarded as a very abundant source of structurally diverse, high molecular weight polysaccharides having variable composition and roles according to the organisms and the environmental conditions in which they are produced. Due to their structural complexity, versatility and valuable biological properties, they are now emerging as high-value compounds. They are possessing exceptional properties and thus are being widely explored for various applications like in food and pharmaceutical industries, in bioremediation for removal of heavy metals, for soil conditioning, as biopolymers, bioadhesives, and bioflocculants. However, poor understanding of their complex structural properties, lack of concrete information regarding the genes encoding the proteins involved in the EPS biosynthetic pathways, their process of production and about the associated factors controlling their structural stability, strongly limits their commercialization and applications in the various fields of biotechnology. Owing to the above context, the present review is aimed to organize the available information on applications of cyanobacterial EPSs in the field of biotechnology and to identify the research gaps for improved industrial utilization and commercialization of these biomaterials.
Polysaccharides obtained from bacteria, fungi, and microalgae can display a wide range of valuable physicochemical characteristics, which have driven the interest toward research of their functional properties. Although most microbial polysaccharides have been studied due to their ability to modify the rheological properties of aqueous media, many of such biopolymers possess biological activities with great potential for treating various diseases. As so, microbial polysaccharides have found use in food, pharmaceutical, medical, and cosmetic applications. Besides their already established uses, microbial polysaccharides are being studied for their potential applications in novel areas, wherein they are advantageous over other synthetic or natural polymers. This chapter addresses some of those emerging applications, including the development of hydrogels and bionanocomposites based on different microbial polysaccharides, as well as the potential demonstrated by chitinous polymers and that of novel polysaccharides isolated from microalgae.
The Euganean Thermal District (Italy) represents the oldest and largest thermal center in Europe, and its therapeutic mud is considered a unique product whose beneficial effects have been documented since Ancient Roman times. Mud properties depend on the heat and electrolytes of the thermal water, as well as on the bioactive molecules produced by its biotic component, mainly represented by cyanobacteria. The investigation of the healing effects of compounds produced by the Euganean cyanobacteria represents an important goal for scientific validation of Euganean mud therapies and for the discovering of new health beneficial biomolecules. In this work, we evaluated the therapeutic potential of exopolysaccharides (EPS) produced by Phormidium sp. ETS05, the most abundant cyanobacterium of the Euganean mud. Specifically, Phormidium EPS resulted in exerting anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models as demonstrated using specific transgenic zebrafish lines and morphometric and expression analyses. Moreover, in vivo and in vitro tests showed no toxicity at all for the EPS concentrations tested. The results suggest that these EPS, with their combined anti-inflammatory and pro-resolution activities, could be one of the most important therapeutic molecules present in the Euganean mud and confirm the potential of these treatments for chronic inflammatory disease recovery.
An exopolysaccharides/calcipotriol (EPS/CPT) emulsion was prepared using bacterial EPS as emulsifier, sunflower oil as an oil phase and CPT as the loaded drug, and the effect of this emulsion on psoriasis vulgaris treatment was evaluated. An EPS composed of mannose (70.56%) and glucose (29.44%) was obtained from the marine mangrove bacteria Bacillus amyloliquefaciens ZWJ (Zhu Wenjing) strain. The EPS has significant emulsifying activity at the concentration of 1.5%. The prepared EPS/CPT emulsion has small and stable particle size, with a drug content of 0.00492%, and good spreading properties. The in vitro drug release results revealed that the emulsion showed a certain sustained release effect. In vitro and in vivo animal experiments show that the EPS/CPT emulsion can effectively treat psoriasis vulgaris by increasing the accumulation of CPT in psoriatic skin lesions and reducing the levels of inflammatory cells and inflammatory factors (TNF and IL6). Additionally, it has a certain effect on reducing the side effects associated with CPT. This study lays a foundation for the research of EPS in the topical application of medical materials and treatment of psoriasis.
Regular bathing in the Blue Lagoon has beneficial effects on psoriasis. Previously, we showed that exopolysaccharides (EPS-Ca) secreted by Cyanobacterium aponinum, a dominating organism in the Blue Lagoon, increased IL-10 secretion by human dendritic cells (DCs). In addition, co-culturing allogeneic CD4+ T cells with DCs matured in the presence of EPS-Ca increased differentiation of T cells into T regulatory cells at the cost of the disease inducing Th17 cells. In the present study, EPS-Ca increased the proportion of DCs expressing CD141, a surface molecule linked to regulatory DCs, and the CD141+ cells secreted more IL-10 than the CD141- cells. EPS-Ca decreased T cell secretion of IL-17, IL-13 and IL-10 and the proportion of T cells expressing the activation marker CD69 that has also been linked to lymphocyte retention. In addition, EPS-Ca reduced keratinocyte secretion of CCL20 and CXCL10, chemokines implicated in recruitment of inflammatory cells. EPS-Ca decreased DC expression of Dectin-1/CLEC7A and SYK, keratinocyte expression of CLEC7A, SYK and CAMP (the gene for LL37), and T cell expression of phosphorylated Zap70. These results indicate that EPS-Ca may induce a regulatory phenotype of DCs, T cells that are less active/inflammatory and less prone to being retained in the skin, and keratinocytes that induce less recruitment of inflammatory cells to the skin and that these effects may be mediated by the effects of EPS-Ca on CLEC7A and SYK. Overall the results indicate that EPS-Ca may be involved in the beneficial effects psoriasis patients experience when bathing in the Blue Lagoon.
The geothermal system of the Araró region, located in the Trans-Mexican Volcanic Belt of México, hosts various hot springs with unique physicochemical characteristics, including temperatures ranging from 45°C to 78°C. The microbial diversity in these hot springs has been explored only by culture-dependent surveys. In this study, we performed metagenomic Illumina MiSeq, and 16S and 18S rRNA pyrosequencing analysis of the microbial life are residing in the microbial mats of the springs called “Tina–Bonita”. Our results show the presence of 186 operational taxonomic units, 99.7% of which belong to bacteria, 0.27% to eukaryotes, and 0.03% to archaea. The most abundant bacterial divisions are the Proteobacteria, Chloroflexi, and Cyanobacteria, which include 105 genera. The ecological indexes indicate that the microbial mats have moderate microbial diversity. An abundant group of genes that participate in photosynthesis, including photosynthetic electron transport, as well as photosystems I and II, were detected. Another cluster of genes was found that participates in sulfur, nitrogen, and methane metabolism. Finally, this phylogenetic and metagenomic analysis revealed an unexpected taxonomic and genetic diversity, expanding our knowledge of microbial life under specific extreme conditions.
The bacterial diversity of the outflows of Polichnitos (Lesvos, Greece) hot spring has been investigated. Cyanobacteria showing high sequence homologies with Phormidium sp. and Cyanobacterium aponinum were found. Members of the Alphaproteobacteria closely related to Rhodobium sp. Albidovulum sp., Rhodobacter sp., Microvigra sp., Nitratireductor sp. and Phaeobacter sp. Gammaproteobacteria, Betaproteobacteria and Firmicutes were represented by members of Idiomarina sp., Marinobacter sp., Shinella sp., Bacillus sp. and Clostridium sp. with sequence homologies ranging from 92% to 100%. Members of the Bacteroidetes and Planctomycetes were represented by sequences of novel phylogenetic linkages exhibiting 87–90% sequence homology with type strains. When the hot spring consortium was cultivated in bioreactor repeated batch culture under photo-autotrophic growth conditions at temperature < 30 °C, Cyanobacterium sp. dominated over Phormidium sp. Cyanobacterium sp. seems to have biotechnological potential since its extracellular broth exhibited a strong insecticidal activity against larvae of Aedes aegypti (a vector of important human diseases) and significant anti-cancer activity against the PC3 human prostate cancer cell line, while its toxicity against human endothelial cells was relatively low.
A form of coccoid cyanobacterium, collected in Euganean thermal springs from cyanobacteria mats and ascribed to the Cyanobacterium genus has been described. Morphological, ultrastructural, pigment composition and molecular data characterizing this taxon are compared with other species included in the genus Cyanobacterium. The phylogenetic position of this strain has been investigated using 16S rDNA and ITS rDNA as molecular markers and the maximum likelihood and neighbour-joining methods. These results suggest that although the isolate shared features with a Japanese thermal strain (Cyanobacterium sp. MBIC10216), it might be considered a different taxon from previously described Cyanobacterium. For this strain the name Cyanobacterium aponinum is proposed.
Cultivation and culture-independent techniques were used to describe the geothermal ecosystem of the Blue Lagoon in Iceland. The lagoon contains both seawater and freshwater of geothermal origin and is extremely high in silica content. Water samples were collected repeatedly in summer and autumn in 2003 and 2005 and in winter 2006 were analyzed for species composition. The study revealed the typical traits of an extreme ecosystem characterized by dominating species and other species represented in low numbers. A total of 35 taxa were identified. The calculated biodiversity index of the samples was 2.1-2.5. The majority (83%) of analyzed taxa were closely related to bacteria of marine and geothermal origin reflecting a marine character of the ecosystem and the origin of the Blue Lagoon hydrothermal fluid. A high ratio (63%) of analyzed taxa represented putative novel bacterial species. The majority (71%) of analyzed clones were Alphaproteobacteria, of which 80% belonged to the Roseobacter lineage within the family of Rhodobacteraceae. Of seven cultivated species, the two most abundant ones belonged to this lineage. Silicibacter lacuscaerulensis was confirmed as a dominating species in the Blue Lagoon. One group of isolates represented a recently identified species within the genus of Nitratireductor within Rhizobiales. This study implies an annually stable and seasonally dynamic ecosystem in the Blue Lagoon.
Allelopathic interactions involving cyanobacteria are being increasingly explored for the pharmaceutical and environmental significance of the bioactive molecules. Among the toxic compounds produced by cyanobacteria, the biosynthetic pathways, regulatory mechanisms, and genes involved are well understood, in relation to biotoxins, whereas the cytotoxins are less investigated. A range of laboratory methods have been developed to detect and identify biotoxins in water as well as the causal organisms these methods vary greatly in their degree of sophistication and the information they provide. Direct molecular probes are also available to detect and (or) differentiate toxic and nontoxic species from environmental samples. This review collates the information available on the diverse types of toxic bioactive molecules produced by cyanobacteria and provides pointers for effective exploitation of these biologically and industrially significant prokaryotes.
The balance between regulatory and effector functions is important for maintaining efficient immune responses, while avoiding autoimmunity. The inflammatory skin disease psoriasis is sustained by the ongoing activation of pathogenic effector T cells. We found that a CD4(+) T lymphocyte subpopulation in peripheral blood, phenotypically CD25(high), CTLA-4(+), Foxp3(high) (regulatory T (Treg) cells), is deficient in its suppressor activity in psoriasis. This was associated with accelerated proliferation of CD4(+) responder T cells in psoriasis, the majority of which expressed CXCR3. Nevertheless, criss-cross experiments isolated the defect to psoriatic Treg cells. To examine Treg cells in a nonlymphoid tissue of a human T cell-mediated disease, Treg cells were also analyzed and isolated from the site of inflammation, psoriatic lesional skin. At the regulatory vs effector T cells ratios calculated to be present in skin, however, the psoriatic Treg cell population demonstrated decreased suppression of effector T cells. Thus, dysfunctional blood and target tissue CD4(+)CD25(high) Treg cell activity may lead to reduced restraint and consequent hyperproliferation of psoriatic pathogenic T cells in vivo. These findings represent a critical component of human organ-specific autoimmune disease and may have important implications with regard to the possible therapeutic manipulation of Treg cells in vivo.
A combined treatment with saltwater baths and narrow-band ultraviolet-B (NB-UVB) is a known treatment for psoriasis. This study evaluates and compares two treatment regimens including bathing in geothermal seawater combined with NB-UVB therapy and a NB-UVB monotherapy.
Sixty-eight psoriasis patients were randomly assigned to bathing in geothermal seawater combined with NB-UVB therapy three times/week, intensive daily treatment of bathing in geothermal seawater combined with NB-UVB therapy or NB-UVB therapy alone three times/week, for 6 weeks. Disease severity (PASI and Lattice score), quality of life (DLQI) and histological changes were evaluated before, during and after treatment. The primary endpoint was the proportion of patients who achieved PASI 75 at 6 weeks.
At 6 weeks, the percentage of patients who achieved PASI 75 and PASI 90 was significantly greater with both bathing in geothermal seawater (68.1%/18.2%) and intensive treatment (73.1%/42.3%) than with NB-UVB monotherapy (16.7%/0%, p<0.05 in all comparisons). Clinical improvement was paralleled with improvement in DQLI, histological score and had a sparing effect on NB-UVB dosages.
Bathing in geothermal seawater combined with NB-UVB therapy induces faster clinical and histological improvement, longer remission time and has a sparing effect on NB-UVB doses than UVB therapy alone in psoriasis.
It is known that NB-UVB therapy can suppress a broad range of immune cells but the additional effect of bathing in geothermal seawater still remains unclear. To study the influence of treatment on the expression of circulating immune cells contributing to the pathogenesis of psoriasis, six psoriasis patients were treated with bathing in geothermal seawater 2 times daily combined with NB-UVB 5 times/week for two weeks and 6 patients were treated with NB-UVB therapy three times/week for 8 weeks. Disease severity (Psoriasis Area and Severity Index; PASI), chemokines, inflammatory cytokines, T cells and Toll-like receptors in the blood and skin samples were evaluated on enrolment (W0) and at 1 (W1), 3 (W3) and 8 (W8) weeks. Compared with healthy controls, psoriasis patients with active disease had significantly higher proportion of peripheral CLA+ T-cells expressing CCR10 and CD103, and T-cells with both Th1/Tc1 (CD4+/CD8+ IFNγ+ or TNFα+ cells) and Th17/Tc17 (CD4+CD45R0+IL-23R+, CD4+/CD8+ IL-17A+ or IL-22+ cells) phenotypes. Both treatments gave a significant clinical effect, however, bathing in geothermal seawater combined with NB-UVB therapy was more effective than NB-UVB therapy alone. This clinical improvement was reflected by a reduction in circulating CLA+ peripheral blood T cells and decreased Th1/Th17 and Tc1/Tc17 inflammatory response. These findings suggest that the inflammatory response in psoriasis is predominantly driven by both CD4+ and CD8+ skin-homing tissue retaining T cells of the Th17/Tc17 lineages. This article is protected by copyright. All rights reserved.
This chapter presents the Gas-Liquid Chromatographic Analysis of Constituent Carbohydrates in Glycoproteins. Application of gas-liquid chromatography (GLC) to the analysis of steroids, fatty acids, Krebs cycle and allied acids, amino acids, and carbohydrates is presented. The conditions of cleavage, derivatization, and GLC provide a quantitative determination of the commonly found glycoprotein sugars, that is, L-arabinose, L-fucose, D-xylose, D-mannose, D-galactose, D-glucose, N-aeetyl-D-galactosamine, N-acetyl-D-glucosamine, and the neuraminic acids as the N-acetyl derivatives. The chapter describes a general procedure, allowing quantitation of the above-mentioned sugar components, along with two modifications. One modification involves cleavage under mild conditions to determine the neuraminic acid and fucose values. The second modification, under more vigorous conditions, involves assessing total recovery of the amino sugars. For some glycoproteins the general procedure determines all the expected components quantitatively, but this cannot be assumed to be the case with all samples until verified by the modifications. The GLC carried out on a dual-column instrument with a flame-ionization detector and the 0-trimethylsilyl (TMS) ether sugar derivatives.
Human blood myeloid DCs can be subdivided into CD1c (BDCA-1)(+) and CD141 (BDCA-3)(+) subsets that display unique gene expression profiles, suggesting specialized functions. CD1c(+) DCs express TLR4 while CD141(+) DCs do not, thus predicting that these two subsets have differential capacities to respond to Escherichia coli. We isolated highly purified CD1c(+) and CD141(+) DCs and compared them to in vitro generated monocyte-derived DCs (MoDCs) following stimulation with whole E. coli. As expected, MoDCs produced high levels of the proinflammatory cytokines TNF, IL-6, and IL-12, were potent inducers of Th1 responses, and processed E. coli-derived Ag. In contrast, CD1c(+) DCs produced only low levels of TNF, IL-6, and IL-12 and instead produced high levels of the anti-inflammatory cytokine IL-10 and regulatory molecules IDO and soluble CD25. Moreover, E. coli-activated CD1c(+) DCs suppressed T-cell proliferation in an IL-10-dependent manner. Contrary to their mouse CD8(+) DC counterparts, human CD141(+) DCs did not phagocytose or process E. coli-derived Ag and failed to secrete cytokines in response to E. coli. These data demonstrate substantial differences in the nature of the response of human blood DC subsets to E. coli.
Pectin type polysaccharides were extracted from the inner bark of Ulmus glabra Huds., using water at 50°C. After redissolving the product by boiling, fractionation into 9 polymers was achieved by a combination of two different ion exchange columns. The three most abundant polymers were isolated and characterized. The polysaccharides appeared to have structural differences. The two fractions Afplc and Bfplc contain galacturonic acid, galactose and rhamnose, while Cfplc in addition contains 3-O-methylgalactose, glucuronic acid and acetyl groups. The backbone of all three polysaccharides consists of 4-linked α-D-galactopyranosyl-uronic acid interspersed with 2-linked α-L-rhamnopyranosyl residues. The side chains on Afplc and Bfplc consist of galactose units attached to C-3 of the rhamnose, while the side chains of Cfplc are mainly linked through C-4 of rhamnose. These include 4-linked 3-O-methylgalactose. After weak acid hydrolysis, 5 acidic oligosaccharides were isolated and characterized.
This review deals with the different glycans produced by cyanobacteria such as reserve polymers, polysaccharides from the cell envelope and exocellular polysaccharides. For each group a description of previous work is reported, quoting all different strains tested, methods of polysaccharide extraction and chemical and physical characterization. In particular, chemical composition and sequence (when known) are reported although inhomogeneity of results reveals that sometimes methods used are outdated. Emphasis is put on exocellular polysaccharides, the most interesting type of polymers from the technological point of view.
In 1986, Mosmann and Coffman identified 2 subsets of activated CD4 T cells, Th1 and Th2 cells, which differed from each other in their pattern of cytokine production and their functions. Our understanding of the importance of the distinct differentiated forms of CD4 T cells and of the mechanisms through which they achieve their differentiated state has greatly expanded over the past 2 decades. Today at least 4 distinct CD4 T-cell subsets have been shown to exist, Th1, Th2, Th17, and iTreg cells. Here we summarize much of what is known about the 4 subsets, including the history of their discovery, their unique cytokine products and related functions, their distinctive expression of cell surface receptors and their characteristic transcription factors, the regulation of their fate determination, and the consequences of their abnormal activation.
Lichens have been used for medicinal purposes throughout the ages, and beneficial claims have to some extent been correlated with their polysaccharide content. Of 13,500 lichen species growing worldwide, less than 100 species have been investigated for polysaccharide content. Lichen polysaccharides are mainly of three different structural types: beta-glucans, alpha-glucans, and galactomannans. In addition, a few complex heteroglycans have recently been described, such as thamnolan, a water-soluble, immunologically active heteroglycan with a novel rhamnopyranosylgalactofuranan type of structure. A number of investigations have been carried out on biological effects of lichen polysaccharides, most notably antitumour, immunomodulating, antiviral, and memory-enhancing effects. The current review summarizes present knowledge on the structural characteristics and biological activity of lichen polysaccrides.
A study on the effect of two of the main factors affecting energy flux in N(2)-fixing cyanobacteria, i.e. light intensity and availability of combined nitrogen, on the synthesis of soluble exopolysaccharides was carried out with three strains of the genus Nostoc (PCC 7413, PCC 7936, and PCC 8113) presenting different capsular polysaccharidic morphologies and released polysaccharide productions. Strains acclimated to diazotrophic and non-diazotrophic conditions were cultured at high and low light intensities in aerated batch cultures. High light intensities enhanced total carbohydrate synthesis in all the strains but growth measured as pigment and protein concentration, total and soluble carbohydrate concentrations presented a strain-dependent response to nitrate availability. When adequately acclimated to the presence of nitrate all the capsulated strains tested became non-capsulated, with no extracellular polysaccharide being produced. Carbon availability can be on the basis of the observed correlation between the synthesis of capsular polysaccharides and diazotrophy. The slime-forming strain Nostoc PCC 7413 was the only one releasing polysaccharides into the surrounding medium under both, diazotrophic and non-diazotrophic conditions, with the highest values being obtained in the presence of nitrate. This strain presented the highest total carbohydrate (3.5 gl(-1)), soluble carbohydrate (1.8 gl(-1)) concentrations and viscosity values of all the tested strains. Different mechanisms of nitrogen-control of the synthesis of exocellular polysaccharides are reported for each strain, which results in the requirement of a species-specific optimisation of the cultivation conditions for the development of an efficient technology for the production of cyanobacterial exopolysaccharides.
Biological response modifiers (BRMs) are substances which augment immune response. BRMs can be cytokines which are produced endogenously in our body by immune cells or derivatives of bacteria, fungi, brown algae, Aloe vera and photosynthetic plants. Such exogeneous derivatives (exogeneous BRMs) can be nucleic acid (CpG), lipid (lipotechoic acid), protein or polysaccharide in nature. The receptors for these exogeneous BRMs are pattern recognition receptors. The binding of exogeneous BRMs to pattern recognition receptors triggers immune response. Exogenous BRMs have been reported to have anti-viral, anti-bacterial, anti-fungal, anti-parasitic, and anti-tumor activities. Among different exogeneous BRMs, polysaccharide BRMs have the widest occurrence in nature. Some polysaccharide BRMs have been tested for their therapeutic properties in human clinical trials. An overview of current understandings of polysaccharide BRMs is summarized in this review.
Recently, a novel and unique subset of interleukin (IL)-17-producing CD4+ T helper (Th17) cells, distinct from Th1 and Th2 cells, was discovered. The question is addressed as to what extent inflammatory skin diseases are associated with the actions of this newly discovered Th17 cell subset.
Th17 cells are involved in protection against bacterial pathogens. In addition, it is now clear that Th17 cells may also be crucial in the pathogenesis of various chronic inflammatory diseases that were formerly categorized as Th1-mediated disorders.
In this review, we summarize the current knowledge of IL-17 and Th17 cells and discuss the possible role of IL-17 in the pathology of psoriasis, contact hypersensitivity and atopic dermatitis. Whereas IL-17 may play an important role in the pathogenesis of psoriasis and contact hypersensitivity, its role in atopic dermatitis is still unclear.
Cetraria islandica (Iceland moss) has been used for centuries in folk medicine in many countries against a number of conditions, including inflammatory conditions, mainly as an aqueous extract. C. islandica contains many compounds, such as polysaccharides and secondary metabolites, some of which have established biological activity. However, very little is known about their effect on the immune system. Human monocyte-derived immature dendritic cells were cultured with an aqueous extract from C. islandica quantified with regard to the polysaccharides lichenan and isolichenan and secondary metabolites protolichesterinic and fumarprotocetraric acids. The purified compounds were also tested individually. Their effect on the maturation of the dendritic cells was assessed by measuring secretion of IL-10 and IL-12p40 and expression of surface molecules. In addition, the effect of the aqueous extract on antigen-induced arthritis in rats was investigated. The aqueous extract caused upregulated secretion of both IL-10 and IL-12p40, with IL-10 secretion being more prominent. Lichenan had similar effects, whereas isolichenan and the secondary metabolites were inactive, suggesting that the effect observed by the aqueous extract was mainly mediated by lichenan. Significantly less arthritis was observed for rats treated by the aqueous extract, administered subcutaneously, compared with rats treated with saline alone. These results suggest that the aqueous extract of C. islandica has anti-inflammatory effect, possibly by changing the cytokine secretion bias from IL-12p40 towards IL-10.
Bathing in the Blue Lagoon, a specific geothermal biotope in Iceland has been known for many years to be beneficial for human skin in general and for patients with psoriasis and atopic dermatitis in particular. The scientific rationale for this empirical observation, however has remained elusive. We now report that extracts prepared from silica mud and two different microalgae species derived from the Blue Lagoon are capable of inducing involucrin, loricrin, transglutaminase-1 and filaggrin gene expression in primary human epidermal keratinocytes. The same extracts also affects primary human dermal fibroblasts, because extracts from silica mud and one type of algae inhibited UVA radiation-induced upregulation of matrix metalloproteinase-1 expression and both algae, as well as silica mud extracts induced collagen 1A1 and 1A2 gene expression in this cell type. These effects were not restricted to the in vitro situation because topical treatment of healthy human skin (n = 20) with a galenic formulation containing all three extracts induced identical gene regulatory effects in vivo, which were associated with a significant reduction of transepidermal water loss. In aggregate, these results suggest that the bioactives in Blue Lagoon have the capacity to improve skin barrier function and to prevent premature skin ageing. These observations explain at least some of the beneficial effects of bathing in the Blue Lagoon and provide a scientific basis for the use of Blue Lagoon extracts in cosmetic and/or medical products.
Dendritic cells (DC) are key regulators of immune responses. Mature DC are traditionally considered to be immunogenic, although there is accumulating evidence that they can also be tolerogenic and induce Ag-specific regulatory T cells (Tregs). However, the mechanism of this Treg induction and the site of Treg action in vivo are yet to be defined. In this study, using the experimental model of interphotoreceptor retinoid-binding protein peptide (1-20)-induced experimental autoimmune uveoretinitis, we show that s.c. inoculation of IRBP-peptide-pulsed IL-10-producing LPS-activated mature DC (IL-10-DC) at one site (the cervical region) suppresses autoimmunity induced at a separate site (the inguinal region). Our data show that s.c. IL-10-DC correlates with an increase in the number of CD4(+)CD25(+)Foxp3(+) Tregs at the DC-draining lymph nodes (DC-dLN). However, although MHCII(-/-) IL-10-DC also induces Treg expansion at this DC-dLN, they failed to suppress experimental autoimmune uveoretinitis. Furthermore, unlike wild-type IL-10-DC, MHCII(-/-) IL-10-DC did not correlate with an increase in the percentage of Tregs expressing CD62L at the DC-dLN, nor did they associate with an increase in Treg number at a distal site. Similar effects were also observed after s.c. hen egg lysozyme-pulsed IL-10-DC, which produced a strong reduction in the number and activation of proliferating Ag-specific CD4(+) 3A9 T effector cells. We therefore propose that IL-10-DC require MHCII-dependent Ag presentation, and hence TCR ligation, to promote CD62L-mediated trafficking of Tregs to the site of T effector cell priming, where they suppress autoimmunity.
Our understanding of the role of T cells in human disease is undergoing revision as a result of the discovery of T-helper 17 (Th17) cells, a unique CD4(+) T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine with robust effects on stromal cells in many tissues. Recent data in humans and mice suggest that Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Initial reports also propose a role for Th17 cells in tumorigenesis and transplant rejection. Important differences, as well as many similarities, are emerging when the biology of Th17 cells in the mouse is compared with corresponding phenomena in humans. As our understanding of human Th17 biology grows, the mechanisms underlying many diseases are becoming more apparent, resulting in a new appreciation for both previously known and more recently discovered cytokines, chemokines, and feedback mechanisms. Given the strong association between excessive Th17 activity and human disease, new therapeutic approaches targeting Th17 cells are highly promising, but the potential safety of such treatments may be limited by the role of these cells in normal host defenses against infection.
Cyanobacterial bioactive molecules – an overview of their toxic properties
- Jaiswal
Interleukin-17 in inflammatory skin disorders
- van Beelen