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Redox sensor NPGPx restrains ZAP70 activity and modulates T cell homeostasis.
Su, Fang-Yi; Huang, Shih-Chia; Wei, Pei-Chi; Hsu, Pang-Hung; Li, Ju-Pi; Su, Li-Wen; Hsieh, Yung-Lin; Hu, Chun-Mei; Hsu, Jye-Lin; Yang, Cheng-Yuan; Chung, Chen-Yen; Shew, Jin-Yuh; Lan, Joung-Liang; Sytwu, Huey-Kang; Lee, Eva Y-Hp; Lee, Wen-Hwa.
Afiliación
  • Su FY; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
  • Huang SC; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Wei PC; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsu PH; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
  • Li JP; Division of Rheumatology and Immunology and Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Su LW; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsieh YL; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hu CM; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsu JL; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Drug Development Research Center, China Medical University, Taichung, Taiwan.
  • Yang CY; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Chung CY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Shew JY; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Lan JL; Division of Rheumatology and Immunology and Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
  • Sytwu HK; Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.
  • Lee EY; Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
  • Lee WH; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Drug Development Research Center, China Medical University, Taichung, Taiwan; Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA. Electronic address: whlee@uci.edu.
Free Radic Biol Med ; 165: 368-384, 2021 03.
Article en En | MEDLINE | ID: mdl-33460768
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Proteómica Límite: Animals Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Proteómica Límite: Animals Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos