國家衛生研究院 NHRI:Item 3990099045/6104
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    題名: DUSP4 deficiency enhances CD25 expression and CD4(+) T-cell proliferation without impeding T-cell development
    作者: Huang, CY;Lin, YC;Hsiao, WY;Liao, FH;Huang, PY;Tan, TH
    貢獻者: Immunology Research Center
    摘要: The differentiation and activation of T cells are critically modulated by MAP kinases, which are in turn feed-back regulated by dual-specificity phosphatases (DUSPs) to determine the duration and magnitude of MAP kinase activation. DUSP4 (also known as MKP2) is a MAP kinase-induced DUSP member that is dynamically expressed during thymocyte differentiation. We generated DUSP4-deficient mice to study the function of DUSP4 in T-cell development and activation. Our results show that thymocyte differentiation and activation-induced MAP kinase phosphorylation were comparable between DUSP4-deficient and WT mice. Interestingly, activated DUSP4−/− CD4+ T cells were hyperproliferative while DUSP4−/− CD8+ T cells proliferated normally. Further mechanistic studies suggested that the hyperproliferation of DUSP4−/− CD4+ T cells resulted from enhanced CD25 expression and IL-2 signaling through increased STAT5 phosphorylation. Immunization of DUSP4−/− mice recapitulated the T-cell hyperproliferation phenotype in antigen recall responses, while the profile of Th1/Th2-polarized antibody production was not altered. Overall, these results suggest that other DUSPs may compensate for DUSP4 deficiency in T-cell development, MAP kinase regulation, and Th1/Th2-mediated antibody responses. More importantly, our data indicate that DUSP4 suppresses CD4+ T-cell proliferation through novel regulations in STAT5 phosphorylation and IL-2 signaling.
    日期: 2012-02
    關聯: European Journal of Immunology. 2012 Feb;42(2):476-488.
    Link to: http://dx.doi.org/10.1002/eji.201041295
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000299337800023
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84862933832
    顯示於類別:[譚澤華] 期刊論文
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