A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses.
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.
Volpe
Elisabetta
E
Institut National de la Santé et de la Recherche Médicale U653, Paris F-75248, France.
Servant
Nicolas
N
Zollinger
Raphaël
R
Bogiatzi
Sofia I
SI
Hupé
Philippe
P
Barillot
Emmanuel
E
Soumelis
Vassili
V
D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D016212:Transforming Growth Factor beta