A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses

Elisabetta Volpe, Nicolas Servant, Raphaël Zollinger, Sofia I. Bogiatzi, Philippe Hupé, Emmanuel Barillot, Vassili Soumelis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)650-657
Number of pages8
JournalNature Immunology
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 2008

ASJC Scopus subject areas

  • Immunology

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