Botond-Zoltán Igyártó

Thomas Jefferson University | Jefferson · Department of Microbiology & Immunology

Billions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. Here we bring experimental evidence that pre-exposure to mRNA-LNPs or its LNP component has effects on both innate and adaptive immune responses. Pre-exposure to mRNA-LNPs led...

Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The...

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that A...

To determine the contribution of skin DC subsets in the regulation of humoral immunity, we used a well-characterized antigen targeting system to limit antigen availability and presentation to certain skin-derived DC subsets. Here we show that delivery of foreign antigen to steady state Langerhans cells (LCs) and cDC1s through the same receptor (Lan...

The immune functions of epithelia-resident dendritic cells are influenced by epithelial-derived cytokines. Here we identified a communication form between tissue-resident dendritic cells and niche cells that allows direct intracellular material exchange between the parties. We show that many keratinocyte (KC)-specific molecules such as keratins and...

This analysis piece will attempt to examine some of the critical pandemic-related measures implemented in the United States from an immunological perspective and pinpoint caveats that should have been considered before their implementation. I also discuss alternative measures grounded in scientific data that were not thoroughly explored and likely...

We describe a protocol to study inflammatory responses triggered by the mRNA-lipid nanoparticle (LNP) vaccine formulations in skin, muscle, and lung and the adaptive immune responses induced in the draining lymph nodes. Here, we will present how to deliver these reagents through intradermal, intramuscular, and intranasal routes, generating single-c...

Thymic presentation of self-antigens is critical for establishing a functional yet self-tolerant T cell population. Hybrid peptides formed through transpeptidation within pancreatic beta cell lysosomes have been proposed as a new class of autoantigens in Type 1 Diabetes (T1D). While the production of hybrid peptides in the thymus has not been explo...

CD40 is a potent activating receptor expressed on antigen-presenting cells (APCs) of the immune system. CD40 regulates many aspects of B and T cell immunity via interaction with CD40L expressed on activated T cells. Targeting antigens to CD40 via agonistic anti-CD40 antibody fusions promotes both humoral and cellular immunity, but current anti-CD40...

CD40 is a potent activating receptor within the TNFR family expressed on APCs of the immune system, and it regulates many aspects of B and T cell immunity via interaction with CD40 ligand (CD40L; CD154) expressed on the surface of activated T cells. Soluble CD40L and agonistic mAbs directed to CD40 are being explored as adjuvants in therapeutic or...

Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The...

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1...

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccines against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in humans that rem...

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against coronavirus disease in 2019 (COVID-19). Clinical trials and ongoing vaccinations present with very high protection levels and varying degrees of side effects. However, the nature of the reported side effects remains poorly...

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccine candidates against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in human...

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells’ biology. However, very little is known about whether the tissue resident immune cells in return also affect the local env...

The production and wide use of artificial antigen presenting cells (aAPCs) in the clinic as cancer immunotherapeutics are hindered by the need of identifying immunogenic cancer antigens and production of recombinant patient-specific major histocompatibility complexes (MHC) loaded with these peptides. To overcome these limitations, in this study, we...

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the niche cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells' biology. However, very little is known about whether the tissue resident immune cells in return also affect the local env...

HuLangerin-Cre-YFPf/f mice were generated to specifically mark a subset of antigen presenting immune cells, called Langerhans cells (LCs). During histological characterization of these mice, we found that, in addition to LCs an uncharacterized cell population in the central nervous system (CNS) also expressed YFP. In this study, we found that the C...

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping pattern...

The contribution of individual subsets of dendritic cells (DCs) to generation of adaptive immunity is central to understanding immune homeostasis and protective immune responses. We sought to define functions for steady-state skin DCs. We present an approach in which we restrict antigen presentation to individual DC subsets in the skin and monitor...

Memory CD8 T cells protect against intracellular pathogens by scanning host cell surfaces; thus, infection detection rates depend on memory cell number and distribution. Population analyses rely on cell isolation from whole organs, and interpretation is predicated on presumptions of near complete cell recovery. Paradigmatically, memory is parsed in...

Highlights d C. albicans yeast, but not filamentous forms, are required for Th17 cell responses d Th17 cell induction requires LC-derived IL-6 and Dectin-1 ligation d Absent Dectin-1 ligation by pseudo-hyphae prevents Th17 cell induction by CD11b + dDCs d Th17 cells provide cutaneous protection and Th1 cells provide systemic protection In Brief Can...

Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103(+) subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103(+)CD11b(+) LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP T...

Langerhans cells (LCs) are skin-resident dendritic cells (DC) located in the epidermis that migrate to skin-draining lymph nodes during the steady state and in response to inflammatory stimuli. TGF-β1 is a critical immune regulator that is highly expressed by LCs. The ability to test the functional importance of LC-derived TGF-β1 is complicated by...

Langerhans cells (LC) are a subset of skin-resident dendritic cells (DC) that reside in the epidermis as immature DC, where they acquire Ag. A key step in the life cycle of LC is their activation into mature DC in response to various stimuli, including epicutaneous sensitization with hapten and skin infection with Candida albicans. Mature LC migrat...

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC exp...

The clarification of cutaneous dendritic cell subset and the role of thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with protein antigens, as in the development of atopic dermatitis, is a crucial issue. Because TSLP is highly expressed in the vicinity of Langerhans cells (LCs), we sought to clarify our hypothesis that L...

The skin is a barrier site that is exposed to a wide variety of potential pathogens. As in other organs, pathogens that invade the skin are recognized by pattern-recognition receptors (PRRs). Recently, it has been recognized that PRRs are also engaged by chemical contact allergens and, in susceptible individuals, this elicits an inappropriate immun...

Listeria monocytogenes infection generates T helper 1 (Th1) effector memory cells and CC chemokine receptor 7 (CCR7)(+) cells resembling central memory cells. We tracked endogenous L. monocytogenes-specific CD4(+) T cells to determine how these memory cells are formed. Two effector cell populations were already present several days after infection....

Skin-resident dendritic cells (DCs) are well positioned to encounter cutaneous pathogens and are required for the initiation of adaptive immune responses. There are at least three subsets of skin DC- Langerhans cells (LC), Langerin(+) dermal DCs (dDCs), and classic dDCs. Whether these subsets have distinct or redundant function in vivo is poorly un...

The success of a non-live vaccine requires improved formulation and adjuvant selection to generate robust T cell immunity following immunization. Here, using protein linked to a TLR7/8 agonist (conjugate vaccine), we investigated the functional properties of vaccine formulation, the cytokines, and the DC subsets required to induce protective multif...

Understanding the function of Langerhans cells (LCs) in vivo has been complicated by conflicting results from LC-deficient mice. Human Langerin-DTA mice constitutively lack LCs and develop exaggerated contact hypersensitivity (CHS) responses. Murine Langerin-diphtheria toxin receptor (DTR) mice allow for the inducible elimination of LCs and Langeri...

Langerhans cells (LC) are dendritic cell that resides in the epidermis of skin. Paul Langerhans originally observed and named this epinonymous cell more than 140 years ago. Their network-like distribution and dendritic processes that extended up into the stratum corneum convinced him that they represented peripheral nerve cells. It was not determin...

Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of...

This paper introduces two novel monoclonal antibodies, designated GTr1 and GTr2, which recognise guinea fowl thrombocyte surface antigen(s). The antibodies were tested in embryos and adult birds. GTr1 and GTr2 staining emerged at embryonic days 12 and 7, respectively. After embryonic day 12 there was no difference in staining pattern between the tw...

Caveolae-mediated endocytosis is a highly regulated endocytic pathway that exists in parallel to other forms of clathrin-dependent and -independent endocytosis. Internalized caveolae accumulate in intermediate organelles called caveosomes. Here we addressed the further fate of internalized caveolae by inducing caveolae-mediated uptake of albumin by...

A panel of monoclonal antibodies was gen- erated against the guinea fowl's bursal cells. One of the antibodies, designated BoA1, recognized both cortical and medullary B cells of bursal follicles and B cell depen- dent regions of peripheral lymphoid organs, like germinal centers and splenic periellipsoidal regions. The staining pattern of this mono...

A panel of monoclonal antibodies was generated against the guinea fowl's bursal cells. One of the antibodies, designated BoA1, recognized both cortical and medullary B cells of bursal follicles and B cell dependent regions of peripheral lymphoid organs, like germinal centers and splenic periellipsoidal regions. The staining pattern of this monoclon...

Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis of the skin and traffic to lymph nodes (LNs). The general role of these cells in skin immune responses is not clear because distinct models of LC depletion resulted in opposite conclusions about their role in contact hypersensitivity (CHS) responses. While comparing th...

According to some researchers, animals show different coping styles to deal with stressful situations. In the case of social carnivores, social stress is a substantial part of the overall stress load. Previous research has established two extreme (proactive and reactive) coping styles in several animal species, but means of coping with social stres...

The ellipsoid-associated cell (EAC) is a blood-borne phagocytic cell, residing in the antigen trapping zone of the chicken spleen. Binding and endocytosis of betaGalactosidase (betaGal) are independent from the Fc and complement receptors, because sulfated polysaccharides, in a concentration manner, inhibit the bacterial antigen uptake. The betaGal...

It has been known for 15 years that the chicken epidermis contains ATPase+ and major histocompatibility complex class II-positive (MHCII+) dendritic cells. These cells were designated as Langerhans cells but neither their detailed phenotype nor their function was further investigated. In the present paper we demonstrate a complete overlapping of AT...

The purpose of this study was to investigate the influence of the cytostatic drug, 5-fluorouracil (5-FU), which causes depletion of heterophil granulocytes, on clinical symptoms and histological lesions during the progress of infectious bursal disease virus (IBDV) infection in chickens. The aim was to disclose the mechanism behind the clinical dise...

The avian bursa of Fabricius has a direct connection to the cloaca via the bursal duct. Using the bursal duct ligation technique, it has been clearly shown that the B cells of the bursal follicles develop under the influence of cloacal antigens. These antigens have been suggested to be present on the bursal secretory dendritic cells in immunoglobul...

The oesophageal tonsil of the chicken is a novel member of the mucosal-associated lymphoid tissue (MALT), which is located around the entrance of the proventriculus. It consists of 6 to 8 single units, which are surrounded by a thin fibrous capsule. Each one is organised around the bottom of the longitudinal folds of the oesophagus, and serves as a...