TY - JOUR
T1 - A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
AU - Volpe, Elisabetta
AU - Servant, Nicolas
AU - Zollinger, Raphaël
AU - Bogiatzi, Sofia I.
AU - Hupé, Philippe
AU - Barillot, Emmanuel
AU - Soumelis, Vassili
PY - 2008/6
Y1 - 2008/6
N2 - Interleukin 17 (IL-17)-producing T helper 17 cells (TH-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (TH1) and TH2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human TH-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-β, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1β and IL-6) were all essential for human TH-17 differentiation. However, individual TH-17 cell-derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global TH-17 cytokine profile, were differentially modulated by TH-17-promoting cytokines. Transforming growth factor-β was critical, and its absence induced a shift from a TH-17 profile to a TH1-like profile. Our results shed new light on the regulation of human TH-17 differentiation and provide a framework for the global analysis of T helper responses.
AB - Interleukin 17 (IL-17)-producing T helper 17 cells (TH-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (TH1) and TH2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human TH-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-β, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1β and IL-6) were all essential for human TH-17 differentiation. However, individual TH-17 cell-derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global TH-17 cytokine profile, were differentially modulated by TH-17-promoting cytokines. Transforming growth factor-β was critical, and its absence induced a shift from a TH-17 profile to a TH1-like profile. Our results shed new light on the regulation of human TH-17 differentiation and provide a framework for the global analysis of T helper responses.
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U2 - 10.1038/ni.1613
DO - 10.1038/ni.1613
M3 - Article
C2 - 18454150
AN - SCOPUS:44049102724
VL - 9
SP - 650
EP - 657
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 6
ER -