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Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Wang Yuman[1] * ; Sun Zaiqiao[2] ; Ping Jieming[1] ; Tang Jianlong[1] ; He Boxiao[2] ; Chang Teding[3] ; Zhou Qian[4] ; Yuan Shijie[1] ; Tang Zhaohui[3] ; Li Xin[5] ; Lu Yan[6] ; He Ran[1] ; He Ximiao[4] ; Liu Zheng[7] ; Yin Lei[4] ; Wu Ning[1,7,8,9] ;
单位： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [2]State KeyLaboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University,Wuhan, China [3]Department of Traumatic Surgery,Tongji Trauma Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science andTechnology,Wuhan,China [4]Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, China [5]Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China [6]Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China [7]Department of Otolaryngology-Head andNeck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [8]Cell Architecture Research Center,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [9]The First Affiliated Hospital of Anhui Medical University, Institute ofClinical Immunology, Anhui Medical University, Hefei, China
出处：
DOI： 10.1038/s41467-023-42817-y
ISSN：

摘要：
Biosynthesis drives the cell volume increase during T cell activation. However, the contribution of cell volume regulation in TCR signaling during T lymphoblast formation and its underlying mechanisms remain unclear. Here we show that cell volume regulation is required for optimal T cell activation. Inhibition of VRACs (volume-regulated anion channels) and deletion of leucine-rich repeat-containing protein 8A (LRRC8A) channel components impair T cell activation and function, particularly under weak TCR stimulation. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles, indicating the prominent effects of cell volume regulation for T cell functions. Moreover, cell volume regulation via LRRC8A controls T cell-mediated antiviral immunity and shapes the TCR repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via regulated volume decrease (RVD) during T cell blast formation to keep the TCR signaling molecules at an adequate density. Together, our results show a further layer of T cell activation regulation that LRRC8A functions as a cell volume controlling "valve" to facilitate T cell activation.© 2023. The Author(s).

基金：
National Natural Science Foundation of China to N. Wu (32370894), the National Key Research and Development Program of China to N. Wu (2021YFC2701200 and 2022YFF0710600).
语种：
外文
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出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
通讯作者：
通讯机构： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [7]Department of Otolaryngology-Head andNeck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [8]Cell Architecture Research Center,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [9]The First Affiliated Hospital of Anhui Medical University, Institute ofClinical Immunology, Anhui Medical University, Hefei, China
推荐引用方式(GB/T 7714)：
Wang Yuman,Sun Zaiqiao,Ping Jieming,et al.Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function[J].NATURE COMMUNICATIONS.2023,14(1):doi:10.1038/s41467-023-42817-y.
APA：
Wang Yuman,Sun Zaiqiao,Ping Jieming,Tang Jianlong,He Boxiao...&Wu Ning.(2023).Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function.NATURE COMMUNICATIONS,14,(1)
MLA：
Wang Yuman,et al."Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function".NATURE COMMUNICATIONS 14..1(2023)

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