Selective Regulatory Function of Socs3 in the Formation of IL-17-secreting T Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 May 16

PMID 16698929

Citations 298

Authors

Zhi Chen

Arian Laurence

Yuka Kanno

Margit Pacher-Zavisin

Bing-Mei Zhu

Cristina Tato

Akihiko Yoshimura

Lothar Hennighausen

John J OShea

Affiliations

Soon will be listed here.

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.

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