학술논문

A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses.
Document Type
Article
Source
Nature Immunology. Jun2008, Vol. 9 Issue 6, p650-657. 8p. 5 Graphs.
Subject
Language
ISSN
1529-2908
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. [ABSTRACT FROM AUTHOR]