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

doi:10.1038/ni.1613

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

Fondazione Santa Lucia

Research output: Contribution to journal › Article › peer-review

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_H1) and T_H2 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-β, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1β 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-β was critical, and its absence induced a shift from a T_H-17 profile to a T_H1-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.

Original language	English
Pages (from-to)	650-657
Number of pages	8
Journal	Nature Immunology
Volume	9
Issue number	6
DOIs	https://doi.org/10.1038/ni.1613
Publication status	Published - Jun 2008

ASJC Scopus subject areas

Immunology

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A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses. / Volpe, Elisabetta; Servant, Nicolas; Zollinger, Raphaël; Bogiatzi, Sofia I.; Hupé, Philippe; Barillot, Emmanuel; Soumelis, Vassili.

In: Nature Immunology, Vol. 9, No. 6, 06.2008, p. 650-657.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Hupé, Philippe

AU - Barillot, Emmanuel

AU - Soumelis, Vassili

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