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Cited by 225Cytokine Signaling Pathways and InteractionsT-cell and B-cell ImmunologyPsoriasis: Treatment and Pathogenesis

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

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Kinjyo, Ichiko, Inoue, Hiromasa, Hamano, Shinjiro, Fukuyama, Satoru, Yoshimura, Takeru, Koga, Keiko, Takaki, Hiromi, Himeno, Kunisuke +3 more·2006·The Journal of Experimental Medicine
DOI 10.1084/jem.20052333PMC PMC2118269
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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.

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  • STAT3 transcriptionally upregulates anti-inflammatory TGF-β1 and IL-10 in CD4+ T cells and helps IL-10-dependent induction of Th3 cells.

    “STAT3 also transcriptionally upregulates anti-inflammatory transforming growth factor (TGF)-β1 and IL-10 in CD4+ T cells”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Kinjyo et al., 2006

    The Results section reports that active STAT3 increased both TGF-β1 and IL-10 production in CD4+ T cells, and shows STAT3 binding to the TGF-β1 promoter. The Discussion says STAT3 may promote Th3 induction and that IL-10 is usually necessary for Th3 induction in vitro. The copy does not establish direct transcriptional upregulation of IL-10 by STAT3 in these cells or demonstrate that STAT3's effect on Th3 induction depends on IL-10. Page numbers were not available in the supplied copy. (LLM, conf=0.83)

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Cited by

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Authors
Kinjyo, I., Inoue, H., Hamano, S., Fukuyama, S., Yoshimura, T., Koga, K., Takaki, H., Himeno, K., Takaesu, G., Kobayashi, T., & Yoshimura, A.
Affiliations
  • Medical Institute of Bioregulation, Kyushu University (JP)
  • 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences,
  • Kyushu University (JP)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2006-04-10
Volume
203
Issue
4
Pages
1021-1031
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20052333
PMC
PMC2118269
OpenAlex
W2148741505
Cited by
225
References
1
Citations by year
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FWCI
11.30
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
SOCS3, T helper cells, STAT3, TGF-β1, IL-10, Th2 polarization, airway hyperresponsiveness, immunoregulatory cytokines, CD4+ T cells
MeSH terms
Suppressor of Cytokine Signaling 3 Protein, Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Promoter Regions, Genetic, Down-Regulation, Up-Regulation, Transforming Growth Factor beta, Interleukin-10, Leishmaniasis, Cutaneous, Leishmania major, Mice, Knockout, Th2 Cells, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice, Transforming Growth Factor beta1

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