Ion channel TRPV2 is critical in enhancing B cell activation and function

作者全名："Li, Cuifeng; Zhao, Meng; Liu, Xiaohang; Li, Yuxin; Xu, Bihua; Zhou, Lina; Sun, Xiaolin; Sun, Wenbo; Kang, Na; Ji, Zhenglin; Li, Tong; An, Haoran; Wang, Fei; Wu, Chuan; Ye, Jing-Ying; Zhang, Jing-Ren; Wang, Qingwen; Zhao, Xiaodong; Li, Zhanguo; Liu, Wanli"

作者地址："[Li, Cuifeng; Zhao, Meng; Liu, Xiaohang; Li, Yuxin; Sun, Wenbo; Kang, Na; Ji, Zhenglin; Li, Tong; Ye, Jing-Ying; Liu, Wanli] Tsinghua Univ, Sch Life Sci,Beijing Tsinghua Changgung Hosp, State Key Lab Membrane Biol,Inst Immunol, China Minist Educ Key Lab Prot Sci,Beijing Key Lab, Beijing, Peoples R China; [Li, Cuifeng; Zhang, Jing-Ren; Li, Zhanguo; Liu, Wanli] Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China; [Xu, Bihua; Wang, Qingwen] Peking Univ, Dept Rheumatism & Immunol, Shenzhen Hosp, Shenzhen, Peoples R China; [Xu, Bihua; Wang, Qingwen] Shenzhen Key Lab Inflammatory & Immunol Dis, Shenzhen, Peoples R China; [Zhou, Lina] Chongqing Med Univ, Dept Pediat Res Inst, Childrens Hosp, Chongqing, Peoples R China; [Zhou, Lina; Zhao, Xiaodong] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders Chongqing, China Int Sci & Technol Cooperat Base Child Dev &, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China; [Sun, Xiaolin; Li, Zhanguo] Peking Univ Peoples Hosp, Dept Rheumatol & Immunol, Beijing, Peoples R China; [Sun, Xiaolin; Li, Zhanguo] Beijing Key Lab Rheumatism Mech & Immune Diag BZ01, Beijing, Peoples R China; [An, Haoran; Zhang, Jing-Ren] Tsinghua Univ, Ctr Infect Dis Res, Sch Med, Beijing, Peoples R China; [Wang, Fei] Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Peoples R China; [Wu, Chuan] NCI, NIH, Expt Immunol Branch, Bethesda, MD USA; [Zhao, Xiaodong] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Liu, WL (通讯作者)，Tsinghua Univ, Sch Life Sci,Beijing Tsinghua Changgung Hosp, State Key Lab Membrane Biol,Inst Immunol, China Minist Educ Key Lab Prot Sci,Beijing Key Lab, Beijing, Peoples R China.; Zhang, JR; Li, ZG; Liu, WL (通讯作者)，Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China.; Wang, QW (通讯作者)，Peking Univ, Dept Rheumatism & Immunol, Shenzhen Hosp, Shenzhen, Peoples R China.; Wang, QW (通讯作者)，Shenzhen Key Lab Inflammatory & Immunol Dis, Shenzhen, Peoples R China.; Zhao, XD (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders Chongqing, China Int Sci & Technol Cooperat Base Child Dev &, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China.; Li, ZG (通讯作者)，Peking Univ Peoples Hosp, Dept Rheumatol & Immunol, Beijing, Peoples R China.; Li, ZG (通讯作者)，Beijing Key Lab Rheumatism Mech & Immune Diag BZ01, Beijing, Peoples R China.; Zhang, JR (通讯作者)，Tsinghua Univ, Ctr Infect Dis Res, Sch Med, Beijing, Peoples R China.; Zhao, XD (通讯作者)，Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China."

来源：JOURNAL OF EXPERIMENTAL MEDICINE

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001166322400001

JCR分区：Q1

影响因子：12.6

年份：2024

卷号：221

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："This study illuminates that TRPV2 augments B cell activation and function through membrane depolarization and cytoskeletal remodeling. Consequently, TRPV2 is implicated in antibody responses and SLE. The study underscores the indispensable role of TRPV2 in immune regulation and potential therapeutic interventions. The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function."

基金机构："Ministry of Science and Technology of China [2021YFC2300500, 2021YFC2302403]; National Natural Science Foundation of China [32141004, 81825010, 81974253]; Beijing Natural Science Foundation [23Z30090]; Shenzhen Medical Research Fund [C2301008]; Key Project of Basic Research of Shenzhen Science and Technology Innovation Commission [JCYJ20200109140203849]; Treatment and Prevention Integration Project of Shenzhen Municipal Health Commission [0102018-2019-YBXM-1499-01-0414]; National Multiple Sclerosis Society Career Transition Award [3059-A-2]; Tsinghua University Spring Breeze Fund; Center for Life Sciences; Institute for Immunology at Tsinghua University; Vanke School of Public Health at Tsinghua University"

基金资助正文："We acknowledge the healthy volunteers for their participation in our study. We thank S.K. Pierce (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA), K. Rajewsky (Immune Regulation and Cancer, Max-Delbruck-Center for Molecular Medicine, Berlin, Germany), M.J. Caterina (John Hopkins University, Baltimore, MD, USA), M. Shlomchik (University of Pittsburgh, Pittsburgh, PA, USA), C. Goodnow (Garvan Institute of Medical Research, Darlinghurst, Australia), and T. Kurosaki and H. Shinohara (WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan) for providing experimental materials.This work was supported by funds from Ministry of Science and Technology of China (grants 2021YFC2300500 and 2021YFC2302403), National Natural Science Foundation of China (32141004 and 81825010 to W. Liu, 81974253 to Q. Wang), Beijing Natural Science Foundation (23Z30090), and Shenzhen Medical Research Fund (C2301008), Key Project of Basic Research of Shenzhen Science and Technology Innovation Commission (JCYJ20200109140203849), Treatment and Prevention Integration Project of Shenzhen Municipal Health Commission (0102018-2019-YBXM-1499-01-0414), and National Multiple Sclerosis Society Career Transition Award (TA 3059-A-2 to C. Wu). This study is also supported by research funds from Tsinghua University Spring Breeze Fund, Center for Life Sciences, Institute for Immunology at Tsinghua University, and Vanke School of Public Health at Tsinghua University."