Article abstract
Nature Immunology 9, 650 - 657 (2008)
Published online: 4 May 2008 | doi:10.1038/ni.1613
A critical function for transforming growth factor-
, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
Elisabetta Volpe1,2, Nicolas Servant3,4,5, Raphaël Zollinger1,2, Sofia I Bogiatzi1,2, Philippe Hupé3,4,5,6, Emmanuel Barillot3,4,5 & Vassili Soumelis1,2
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-
, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1 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- 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.
- Institut National de la Santé et de la Recherche Médicale U653, Paris F-75248, France.
- Institut Curie, Laboratoire d'Immunologie Clinique, Paris F-75248, France.
- Institut Curie, Bioinformatique, Paris F-75248, France.
- Institut National de la Santé et de la Recherche Médicale, U900, Paris F-75248, France.
- Ecole des Mines de Paris, ParisTech, Fontainebleau F-77300, France.
- Centre National de la Recherche Scientifique, UMR144, Paris F-75248, France.
Correspondence to: Vassili Soumelis1,2 e-mail: vassili.soumelis@curie.net
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