TGF-β promotes Th17 cell development through inhibition of SOCS3

Hongwei Qin*, Lanfang Wang, Ting Feng, Charles O. Elson, Sandrine A. Niyongere, Sun Jung Lee, Stephanie L. Reynolds, Casey T. Weaver, Kevin Roarty, Rosa Serra, Etty N. Benveniste, Yingzi Cong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

TGF-β, together with IL-6 and IL-21, promotes Th17 cell development. IL-6 and IL-21 induce activation of STAT3, which is crucial for Th17 cell differentiation, as well as the expression of suppressor of cytokine signaling (SOCS)3, a major negative feedback regulator of STAT3-activating cytokines that negatively regulates Th17 cells. However, it is still largely unclear how TGF-β regulates Th17 cell development and which TGF-β signaling pathway is involved in Th17 cell development. In this report, we demonstrate that TGF-β inhibits IL-6- and IL-21-induced SOCS3 expression, thus enhancing as well as prolonging STAT3 activation in naive CD4 +CD25- T cells. TGF-β inhibits IL-6-induced SOCS3 promoter activity in T cells. Also, SOCS3 small interfering RNA knockdown partially compensates for the action of TGF-β on Th17 cell development. In mice with a dominant-negative form of TGF-β receptor II and impaired TGF-β signaling, IL-6-induced CD4+ T cell expression of SOCS3 is higher whereas STAT3 activation is lower compared with wild-type B6 CD4 + T cells. The addition of a TGF-β receptor I kinase inhibitor that blocks Smad-dependent TGF-β signaling greatly, but not completely, abrogates the effect of TGF-β on Th17 cell differentiation. Our data indicate that inhibition of SOCS3 and, thus, enhancement of STAT3 activation is at least one of the mechanisms of TGF-β promotion of Th17 cell development.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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