Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1

Ichiko Kinjyo, Hiromasa Inoue, Shinjiro Hamano, Satoru Fukuyama, Takeru Yoshimura, Keiko Koga, Hiromi Takaki, Kunisuke Himeno, Giichi Takaesu, Takashi Kobayashi, Akihiko Yoshimura

研究成果: Contribution to journalArticle査読

168 被引用数 (Scopus)

抄録

Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator of signal transducer and activator of transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic diseases. To define the physiological roles of SOCS3 in T cells, we generated T cell-specific SOCS3 conditional knockout mice. We found that the mice lacking SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced airway hyperresponsiveness but also to Leishmania major infection. In vitro, SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-β1 and interleukin (IL)-10, but less IL-4 than control T cells, suggesting preferential Th3-like differentiation. We found that STAT3 positively regulates TGF-β1 promoter activity depending on the potential STAT3 binding sites. Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was recruited to the TGF-β1 promoter in SOCS3-deficient T cells than in control T cells. The activated STAT3 enhanced TGF-β1 and IL-10 expression in T cells, whereas the dominant-negative form of STAT3 suppressed these. From these findings, we propose that SOCS3 regulates the production of the immunoregulatory cytokines TGF-β1 and IL-10 through modulating STAT3 activation.

本文言語英語
ページ(範囲)1021-1031
ページ数11
ジャーナルJournal of Experimental Medicine
203
4
DOI
出版ステータス出版済み - 4 17 2006

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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