Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells

Zhi Chen, Arian Laurence, Yuka Kanno, Margit Pacher-Zavisin, Bing Mei Zhu, Cristina Tato, Akihiko Yoshimura, Lothar Hennighausen, John J. O'Shea

Research output: Contribution to journalArticle

481 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (Socs) 3 is a cytokine-inducible inhibitor with critical but selective cell-specific effects. We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, Socs3 had no effect on IL-12-dependent signal transducer and activator of transcription (Stat) 4 phosphorylation or IL-4-dependent Stat6 phosphorylation. By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters. We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation.

Original languageEnglish
Pages (from-to)8137-8142
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number21
DOIs
Publication statusPublished - 2006 May 23
Externally publishedYes

Keywords

  • Signal transducer and activator of transcription 3
  • T lymphocytes

ASJC Scopus subject areas

  • General

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