title: A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U653, Paris F-75248, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.forename: Raphaël
authors.initials: R
authors.lastname: Zollinger
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Bogiatzi
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
mesh_terms: 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*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D016212:Transforming Growth Factor beta