RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3-and FADD-mediated cell death  

作　　者：Xiaoxue Deng Lingxia Wang Yunze Zhai Qiuyue Liu Fengxue Du Yu Zhang Wenxing Zhao Tingtao Wu Yiwen Tao Jie Deng Yongbing Cao Pei Hao Jiazi Ren Yunli Shen Zuoren Yu Yuejuan Zheng Haibing Zhang Haikun Wang 

机构地区：[1]State Key Laboratory of Cardiology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,200120,China [2]CAS Key Laboratory of Molecular Virology and Immunology,Shanghai Institute of Immunity and Infection,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai,200031,China [3]CAS Key Laboratory of Nutrition,Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,200031,China [4]The Research Center for Traditional Chinese Medicine,Shanghai Institute of Infectious Diseases and Biosecurity,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [5]Institute of Vascular Disease,Shanghai TCM-Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,200433,China

出　　处：《Cellular & Molecular Immunology》2024年第1期80-90,共11页中国免疫学杂志（英文版）

基　　金：supported by the following grants:National Key Research and Development Program of China(2021YFA1301402);Shanghai Municipal Science and Technology Major Project(ZD2021CY001);National Key Research and Development Program of China(2021YFE0200900,2022YFA0807300);National Natural Science Foundation of China(82101833,82073901);Three-year Action Plan for Shanghai TCM Development and Inheritance Program[ZY(2021-2023)-0103];Top-level Clinical Discipline Project of Shanghai Pudong District(grant/award number:PWYgf 2021-01);Training Plan for Discipline Leaders of Shanghai Pudong New Area Health Commission(grant/award number:PWRd2020-09).

摘　　要：Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely understood.Here,we report that RIPK1 is crucial for T_(reg) cell survival and homeostasis.We generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death.Unlike conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis.However,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways.Thus,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.

关 键 词：Treg cell HOMEOSTASIS Apoptosis NECROPTOSIS 

分 类 号：R392[医药卫生—免疫学]