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 - Tập 103 Số 21 - Trang 8137-8142 - 2006
Zhi Chen1, Arian Laurence1, Yuka Kanno1, Margit Pacher‐Zavisin2, Bing Zhu2, Cristina M. Tato1, Akihiko Yoshimura3, Lothar Hennighausen2, John J. O’Shea1
1*Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and
2Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and
3Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

Tóm tắt

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 theIL-17AandIL-17Fpromoters. 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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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 21

8137-8142

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