國家衛生研究院 NHRI:Item 3990099045/6104
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/6104
    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6104


    Title: DUSP4 deficiency enhances CD25 expression and CD4(+) T-cell proliferation without impeding T-cell development
    Authors: Huang, CY;Lin, YC;Hsiao, WY;Liao, FH;Huang, PY;Tan, TH
    Contributors: Immunology Research Center
    Abstract: 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.
    Date: 2012-02
    Relation: 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
    Appears in Collections:[Tse-Hua Tan] Periodical Articles
    [Ching-Yu Huang] Periodical Articles

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