A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses

Nat Immunol. 2008 Jun;9(6):650-7. doi: 10.1038/ni.1613. Epub 2008 May 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / immunology*
  • Cytokines / metabolism
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-23 / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Transforming Growth Factor beta / metabolism*


  • Cytokines
  • Interleukin-17
  • Interleukin-23
  • Transforming Growth Factor beta