國家衛生研究院 NHRI:Item 3990099045/10968
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 906304      Online Users : 871
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10968


    Title: DUSP6 regulates follicular helper T cell differentiation and T cell metabolism via distinct pathways
    Authors: Chen, MY;Hsu, WC;Su, YW
    Contributors: Immunology Research Center
    Abstract: DUSP6 has been demonstrated to restrict T helper 1 (T H 1) cell differentiation through regulation of ERK1/2-phosphorylation. Here we reported novel roles of DUSP6 in the regulation of follicular helper T (T FH ) cell differentiation and T cell metabolism utilizing DUSP6 knockout (KO) mice. Under T FH cell-differentiation condition, DUSP6-deficient CD4 + T cells produced increased amounts of IL-21, the determinant cytokine directing T FH cell generation. The population of T FH cells increased in the steady state in KO mice, which were associated with an increase of germinal center (GC) B cells. Remarkably, DUSP6-deficient T cells showed a stronger T cell receptor (TCR)-mediated JNK- and p38-phosphorylation. Meanwhile, TCR-in-duced ERK-phosphorylation was marginally affected. Treatment wit DUSP6 inhibitor in Jurkat T cells led to increases of TCR-mediated JNK-and p38-phosphorylation, suggesting that DUSP6 preferentially targeted JNK and p38 in T cells. The increased production of IL-21 in DUSP6-deficient T cells was significantly abolished with the supplement of JNK inhibitor or p38 inhibitor. Unexpectedly, DUSP6-deficient T cells exhibited an impaired glycolysis in the steady state and upon TCR-stimulation. The impaired glycolysis in DUSP6-deficient T cells was not caused by the stronger TCR-mediated JNK- or p38-activation, but due to an impaired activity of phosphofructokinase (PFK), which catalyzes the rate limiting step in the glycolysis pathway. Different than WT T cells, DUSP6-deficient T cells showed a stronger energy fueldependence on glutamine and/or fatty acid. Our data suggest that DUSP6 plays essential roles in effector T cell differentiation and T cell metabolism in various aspects. First, DUSP6 suppresses TCR-mediated JNK- and p38-activation that restrains T FH cell differentiation in the steady state. Secondly, DUSP6 is positively required for the maximal induction of TCR-mediated PFK activation and glycolysis. Thirdly, TCR-induced glycolysis is dispensable for T FH cell differentiation, as long as the alternative energy source such as glutamine or fatty acid is available.
    Date: 2017-12
    Relation: Cytokine. 2017 Dec;100(S1):174.
    Link to: https://doi.org/10.1016/j.cyto.2017.09.011
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1043-4666&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000414817600513
    Appears in Collections:[Yu-Wen Su] Conference Papers/Meeting Abstract

    Files in This Item:

    File Description SizeFormat
    ISI000414817600513.pdf51KbAdobe PDF316View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback