國家衛生研究院 NHRI:Item 3990099045/11326
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    NHRI > Immunology Research Center > Yu-Wen Su > Periodical Articles >  Item 3990099045/11326


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11326


    Title: DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation
    Authors: Hsu, WC;Chen, MY;Hsu, SC;Huang, LR;Kao, CY;Cheng, WH;Pan, CH;Wu, MS;Yu, GY;Hung, MS;Leu, CM;Tan, TH;Su, YW
    Contributors: Immunology Research Center;Institute of Molecular and Genomic Medicine;Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology
    Abstract: Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6(-/-)), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6(-/-) CD4(+) TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6(-/-) mice and in transgenic OTII-DUSP6(-/-) mice at steady state. After immunization, DUSP6(-/-) and OTII-DUSP6(-/-) mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6(-/-) T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6(-/-) T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6(-/-) T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6(-/-) TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.
    Date: 2018-08-21
    Relation: Proceedings of the National Academy of Sciences of the United States of America. 2018 Aug 21;115(34):E8027-E8036.
    Link to: http://dx.doi.org/10.1073/pnas.1800076115
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000442351000021
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85051812351
    Appears in Collections:[Yu-Wen Su] Periodical Articles
    [Tse-Hua Tan] Periodical Articles
    [Cheng-Yuan Gao] Periodical Articles
    [Li-Rung Huang] Periodical Articles
    [Ming-Shiu Hung] Periodical Articles
    [Guann-Yi Yu] Periodical Articles
    [Chien-Hsiung Pan] Periodical Articles
    [Shu-Ching Hsu] Periodical Articles

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