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

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1021-1031
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
Publication statusPublished - 2006 Apr 17
Externally publishedYes

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Transforming Growth Factors
Helper-Inducer T-Lymphocytes
Interleukin-10
T-Lymphocytes
Cytokines
Leishmania major
STAT3 Transcription Factor
Th2 Cells
Chromatin Immunoprecipitation
Ovalbumin
Knockout Mice
Interleukin-4
Transgenic Mice
Hypersensitivity
Binding Sites
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1. / Kinjyo, Ichiko; Inoue, Hiromasa; Hamano, Shinjiro; Fukuyama, Satoru; Yoshimura, Takeru; Koga, Keiko; Takaki, Hiromi; Himeno, Kunisuke; Takaesu, Giichi; Kobayashi, Takashi; Yoshimura, Akihiko.

In: Journal of Experimental Medicine, Vol. 203, No. 4, 17.04.2006, p. 1021-1031.

Research output: Contribution to journalArticle

Kinjyo, I, Inoue, H, Hamano, S, Fukuyama, S, Yoshimura, T, Koga, K, Takaki, H, Himeno, K, Takaesu, G, Kobayashi, T & Yoshimura, A 2006, 'Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1', Journal of Experimental Medicine, vol. 203, no. 4, pp. 1021-1031. https://doi.org/10.1084/jem.20052333
Kinjyo, Ichiko ; Inoue, Hiromasa ; Hamano, Shinjiro ; Fukuyama, Satoru ; Yoshimura, Takeru ; Koga, Keiko ; Takaki, Hiromi ; Himeno, Kunisuke ; Takaesu, Giichi ; Kobayashi, Takashi ; Yoshimura, Akihiko. / Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 4. pp. 1021-1031.
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