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

468 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

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Interleukin-17
Interleukin-23
Phosphorylation
T-Lymphocytes
STAT4 Transcription Factor
Cytokines
Interleukin-12
Interleukin-4

Keywords

  • Signal transducer and activator of transcription 3
  • T lymphocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. / Chen, Zhi; Laurence, Arian; Kanno, Yuka; Pacher-Zavisin, Margit; Zhu, Bing Mei; Tato, Cristina; Yoshimura, Akihiko; Hennighausen, Lothar; O'Shea, John J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 21, 23.05.2006, p. 8137-8142.

Research output: Contribution to journalArticle

Chen, Z, Laurence, A, Kanno, Y, Pacher-Zavisin, M, Zhu, BM, Tato, C, Yoshimura, A, Hennighausen, L & O'Shea, JJ 2006, 'Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 21, pp. 8137-8142. https://doi.org/10.1073/pnas.0600666103
Chen, Zhi ; Laurence, Arian ; Kanno, Yuka ; Pacher-Zavisin, Margit ; Zhu, Bing Mei ; Tato, Cristina ; Yoshimura, Akihiko ; Hennighausen, Lothar ; O'Shea, John J. / Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 21. pp. 8137-8142.
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