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

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135 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
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Qin, H., Wang, L., Feng, T., Elson, C. O., Niyongere, S. A., Lee, S. J., Reynolds, S. L., Weaver, C. T., Roarty, K., Serra, R., Benveniste, E. N., & Cong, Y. (2009). TGF-β promotes Th17 cell development through inhibition of SOCS3. Journal of Immunology, 183(1), 97-105. https://doi.org/10.4049/jimmunol.0801986