Autophagy receptor CCDC50 tunes the STING-mediated interferon response in viral infections and autoimmune diseases
作者机构：MOE Key Laboratory of Tropical Disease ControlCentre for Infection and Immunity Study(CIIS)School of MedicineSun Yat-sen UniversityShenzhenChina The Center for Applied GenomicsAbramson Research CenterThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA Division of RheumatologyThird Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2021年第18卷第10期
页 面：2358-2371页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This study is supported by the National Natural Science Foundation of China(#81620108020 to DG and#81801574 to PH) Guangdong Province"Pearl River Talent Plan"Innovation and Entrepreneurship Team Project(2019ZT08Y464 to CL) Shenzhen Science and Technology Program(#JCYJ20200109142201695 and#KQTD20180411143323605 to DG and#JCYJ20190807161415336 to PH) DG is also supported by the Guangdong Zhujiang Talents Programme and the National Ten-thousand Talents Programme
主 题：CCDC50 STING Type I IFN HSV-1 Autophagy Autoimmune diseases
摘 要：DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal ***,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately *** is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA ***,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for *** of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory ***50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with ***,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune ***50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE ***50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE ***,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.
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