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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    • "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.
    Clinical and Developmental Immunology 07/2013; 2013(9):267971. DOI:10.1155/2013/267971 · 2.93 Impact Factor
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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.
    Journal of Cellular Biochemistry 06/2012; 113(6):2122-5. DOI:10.1002/jcb.24083 · 3.26 Impact Factor
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    • "Insights about IL17F and its potential role at the placentation site are limited. IL17F is proinflammatory with prominent effects on immune and vascular cells [74-76]. Whether IL17F contributes to the organization of the hemochorial placentation site remains to be determined. "
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    ABSTRACT: The trophoblast lineage arises as the first differentiation event during embryogenesis. Trophoblast giant cells are one of several end-stage products of trophoblast cell differentiation in rodents. These cells are located at the maternal-fetal interface and are capable of invasive and endocrine functions, which are necessary for successful pregnancy. Rcho-1 trophoblast stem cells can be effectively used as a model for investigating trophoblast cell differentiation. In this report, we evaluated the role of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in the regulation of trophoblast cell differentiation. Transcript profiles from trophoblast stem cells, differentiated trophoblast cells, and differentiated trophoblast cells following disruption of PI3K signaling were generated and characterized. Prominent changes in gene expression accompanied the differentiation of trophoblast stem cells. PI3K modulated the expression of a subset of trophoblast cell differentiation-dependent genes. Among the PI3K-responsive genes were those encoding proteins contributing to the invasive and endocrine phenotypes of trophoblast giant cells. Genes have been identified with differential expression patterns associated with trophoblast stem cells and trophoblast cell differentiation; a subset of these genes are regulated by PI3K signaling, including those impacting the differentiated trophoblast giant cell phenotype.
    BMC Developmental Biology 09/2010; 10(1):97. DOI:10.1186/1471-213X-10-97 · 2.67 Impact Factor
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