國家衛生研究院 NHRI:Item 3990099045/13171
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    题名: Redox sensor NPGPx restrains ZAP70 activity and modulates T cell homeostasis
    作者: Su, FY;Huang, SC;Wei, PC;Hsu, PH;Li, JP;Su, LW;Hsieh, YL;Hu, CM;Hsu, JL;Yang, CY;Chung, CY;Shew, JY;Lan, JL;Sytwu, HK;E, YHL;Lee, WH
    贡献者: National Institute of Infectious Diseases and Vaccinology
    摘要: Emerging evidences implicate the contribution of ROS to T cell activation and signaling. The tyrosine kinase, ζ-chain-associated protein of 70 kDa (ZAP70), is essential for T cell development and activation. However, it remains elusive whether a direct redox regulation affects ZAP70 activity upon TCR stimulation. Here, we show that deficiency of non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), a redox sensor, results in T cell hyperproliferation and elevated cytokine productions. T cell-specific NPGPx-knockout mice reveal enhanced T-dependent humoral responses and are susceptible to experimental autoimmune encephalomyelitis (EAE). Through proteomic approaches, ZAP70 is identified as the key interacting protein of NPGPx through disulfide bonding. NPGPx is activated by ROS generated from TCR stimulation, and modulates ZAP70 activity through redox switching to reduce ZAP70 recruitment to TCR/CD3 complex in membrane lipid raft, therefore subduing TCR responses. These results reveal a delicate redox mechanism that NPGPx serves as a modulator to curb ZAP70 functions in maintaining T cell homeostasis.
    日期: 2021-03
    關聯: Free Radical Biology and Medicine. 2021 Mar;165:368-384.
    Link to: http://dx.doi.org/10.1016/j.freeradbiomed.2021.01.013
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0891-5849&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000631979100002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85100760762
    显示于类别:[司徒惠康] 期刊論文

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