| Requirements of transcription factor Smad-dependent and -independent TGF-β signaling to control discrete T-cell functions. | |
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MedLine Citation:
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PMID: 22219364 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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TGF-β modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-β achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-β signaling for T-cell function. Smad2 and Smad3 double deficiency in T cells led to lethal inflammatory disorder in mice. Non-Treg cells were spontaneously activated and produced effector cytokines in vivo on deletion of both Smad2 and Smad3. In addition, TGF-β failed to suppress T helper differentiation efficiently and to promote induced Treg generation of non-Treg cells lacking both Smad2 and Smad3, suggesting that Smad-dependent signaling is obligatory to mediate TGF-β function in non-Treg cells. Unexpectedly, however, the development, homeostasis, and function of Treg cells remained intact in the absence of Smad2 and Smad3, suggesting that the Smad-independent pathway is important for Treg function. Indeed, Treg-specific deletion of TGF-β-activated kinase 1 led to failed Treg homeostasis and lethal immune disorder in mice. Therefore, Smad-dependent and -independent TGF-β signaling discretely controls non-Treg and Treg function to modulate immune tolerance and immune homeostasis. |
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Authors:
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Ai-Di Gu; Yunqi Wang; Lin Lin; Song S Zhang; Yisong Y Wan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-4 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: - ISSN: 1091-6490 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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