A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
Abstract
Interleukin 17 (IL-17)-producing T helper 17 cells (T(H)-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T(H)-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-beta, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1beta and IL-6) were all essential for human T(H)-17 differentiation. However, individual T(H)-17 cell-derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global T(H)-17 cytokine profile, were differentially modulated by T(H)-17-promoting cytokines. Transforming growth factor-beta was critical, and its absence induced a shift from a T(H)-17 profile to a T(H)1-like profile. Our results shed new light on the regulation of human T(H)-17 differentiation and provide a framework for the global analysis of T helper responses.
Key Biomarkers
Cited By (18)
- Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of TH-17 responsesPLoS ONE · 2010
- IFN-β Inhibits Human Th17 Cell DifferentiationThe Journal of Immunology · 2009
- Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseasesJapanese Journal of Clinical Immunology · 2010
- Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel diseaseJournal of Clinical Immunology · 2010
- IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel diseaseAnnual Review of Medicine · 2009
- T helper 17 cell heterogeneity and pathogenicity in autoimmune diseaseTrends in Immunology · 2011
- Properties and origin of human Th17 cells
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