Cytokine mediators of Th17 function

Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethsda, MD, USA.
European Journal of Immunology (Impact Factor: 4.03). 03/2009; 39(3):658-61. DOI: 10.1002/eji.200839066
Source: PubMed


Th17 cells were identified as an independent lineage of CD4(+) T cells that secrete a distinctive set of immunoregulatory cytokines, including IL-17A, IL-17F, IL-22, and IL-21. These cytokines collectively play roles in inflammation and autoimmunity and in response to extracellular pathogens. The expression of the lineage-specific transcription factor RORgammat leads to Th17 lineage commitment; however, it has become increasingly clear that the population of cells designated as Th17 cells is not homogeneous. Although these cells collectively produce characteristic Th17 cytokines, not all are produced by each individual cell in the population. The cytokines produced by individual cells are presumably affected in part by the specific local cytokine milieu. In this review, we discuss the current understanding of the specific functional characteristics and regulation of Th17 cytokines and clarify how they mediate the actions of Th17 cells.

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    • "Curiously, IL- 21 is not required for CD8 + T cells development but promotes their cytotoxic functions and memory phenotype generation (Sutherland et al., 2013). IL-21 contributes to the differentiation of CD4 + T cells in Th17 subset by induction of the expression of ROR-gt, a master transcription factor regulator for that phenotype, and consequently, leading to an inflammatory response (Spolski and Leonard, 2009; Raveney et al., 2013; Sutherland et al., 2013). In addition, IL-21 is decisive to the development of Tfh cells and differentiation of activated B cells into plasma cells in germinal centers (Linterman et al., 2010). "
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    ABSTRACT: Interleukin (IL)-21 has been intensively studied for use in therapy of autoimmune diseases, cancers, and chronic viruses due to its immunomodulatory properties, especially on CD4(+) and CD8(+) T cells and natural killer (NK) cells. The objective of this study was to produce an optimized form of IL-21 with improved stability. Plasmids encoding the murine IL-21 alone (pIL-21) or IL-21 genetically fused to portions from mouse IgG3 (pIL-21/Ig) were constructed, and the efficiency of expression, protein kinetics, biodisponibility, and function were analyzed. The genetic constructions of pIL-21 and pIL-21/Ig were transfected into HEK 293 cells, and significant levels of functional IL-21 were obtained. The amino acid of murine IL-21 and IgG3 cloned showed 100% identity with correspondent published sequences. At 24 h of incubation, increased levels of IL-21 were detected in the supernatants of pIL-21. At 72 h of culture, the levels of IL-21 in the supernatant of cells transfected with pIL-21/Ig were significantly higher than those secreted by pIL-21-transfected cells. Furthermore, the data showed that our chimeric IL-21/Ig present improved systemic disponibility in BALB/c mice and conserved the intrinsic ability to increase the frequency of CD4(+) T cells, NKT cells, and CD8(+) T cells.
    Full-text · Article · Dec 2015 · DNA and cell biology
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    • "Th17 cells produce proinflammatory cytokines [3, 4] such as IL-17A, IL-17F, IL-22, IL-26, tumor necrosis factor-α (TNF-α), chemokine (C–C motif) ligand 20 (CCL20) [5], and granulocyte macrophage colony-stimulating factor (GM-CSF) [6]. Although these cytokines all have proinflammatory features, they act on different target cells and therefore contribute to different diseases [7–9]. Th17 cells have been implicated in a wide variety of inflammatory conditions, such as autoimmune diseases, chronic inflammation, and pathogen infection [10]. "
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    ABSTRACT: The significance of Th17 cells and interleukin- (IL-)17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Numerous studies have indicated that Th17 cells and its signature cytokine IL-17A are critical to the airway's immune response against various bacteria and fungal infection. Cytokines such as IL-23, which are involved in Th17 differentiation, play a critical role in controlling Klebsiella pneumonia (K. pneumonia) infection. IL-17A acts on nonimmune cells in infected tissues to strengthen innate immunity by inducing the expression of antimicrobial proteins, cytokines, and chemokines. Mice deficient in IL-17 receptor (IL-17R) expression are susceptible to infection by various pathogens. In this review, we summarize the recent advances in unraveling the mechanism behind Th17 cell differentiation, IL-17A/IL-17R signaling, and also the importance of IL-17A in pulmonary infection.
    Full-text · Article · Jul 2013 · Clinical and Developmental Immunology
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    • "This effector T cell subset appears to be also involved in tumor immunology, but plays dual roles in promoting or discouraging cancer development [Zamarron and Chen, 2011]. A range of cytokines, including TGFb, IL-6, IL-21, IL-23, and IL- 1b, have been shown to participate in the generation of Th17 cells [Spolski and Leonard, 2009]. "
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    ABSTRACT: Little is known about specific IL-23 alterations associated with breast cancer and the data available are still controversial. Therefore, the evaluation of changes in serum IL-23 levels may add further information on the role of this cytokine in breast cancer patients. The aim of this study was to evaluate prospectively the prognostic importance of circulating IL-23 in patients with untreated breast cancer, respect to healthy controls, and the association with clinico-pathological variables. The study involved 50 women diagnosed with stages I-IV breast cancer and 38 healthy controls. Of the 50 breast cancer patients, 37 women were recruited prior to their initial adjuvant chemotherapy and 13 prior to receive first line chemotherapy for metastatic disease. Adjuvant chemotherapy patients were at least in their 4th week post-surgery. IL-23 serum concentrations were measured by a quantitative enzyme immunoassay technique. We found a statistically significant higher systemic cytokine value in women with cancer in comparison with the control group (14.52±11.39 pg/ml vs. 6.35±4.63 pg/ml, P<0.0001). Patients with shorter overall survival presented higher IL-23 values, suggesting a negative prognostic correlation. There was no significant differences in IL-23 levels among patients according to the biomolecular characteristics, the different subtypes and the presence of metastatic disease. This work investigated, for the first time, the role of IL-23 in breast cancer patients showing a significant increase respect the control group. However, further validations are needed in larger studies to better investigate the implications of IL-23 increase in these patients.
    Full-text · Article · Jun 2012 · Journal of Cellular Biochemistry
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