Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function

作     者：Juan Huang Jian Peng James Alexander Pearson Georgios Efthimiou Youjia Hu Ningwen Tai Yanpeng Xing Luyao Zhang Jianlei Gu Jianping Jiang Hongyu Zhao Zhiguang Zhou F.Susan Wong Li Wen 

作者机构：National Clinical Research Center for Metabolic DiseasesKey Laboratory of Diabetes Immunology(Central South University)Ministry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina Section of EndocrinologyDepartment of Internal MedicineSchool of MedicineYale UniversityNew HavenCTUSA Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiffUK Department of MicrobiologyUniversity of HullHullUK Department of Gastrointestinal Surgery of the First Hospital of Jilin UniversityChangchunJilinChina Department of BiostatisticsData Science&GeneticsYale School of Public HealthNew HavenCTUSA 

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2期

页      面：328-338页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 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 work was supported by the National Institutes of Health(DK 045735,HD 097808,Diabetes Action Research and Education Foundation to L.W.) the Diabetes Research Connection(to Y.H.and L.W.),a JDRF Postdoctoral Research Fellowship(3-PDF-2016-197-A-N,2016-2019)and a Medical Research Council Career Development Award(MR/T010525/1 to J.A.P.) This work was supported by funding support from the National Institutes of Health(NIH),Juvenile Diabetes Research Foundation(JDRF),and Medical Research Council(MRC) 

主　　题：Type 1 diabetes Toll-like receptor 7 B cell 

摘      要：Innate immunity mediated by Toll-like receptors(TLRs),which can recognize pathogen molecular patterns,plays a critical role in type 1 diabetes ***7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells;however,its role in type 1 diabetes development remains *** our study,we discovered that Tlr7-deficient(Tlr7^(−/−))nonobese diabetic(NOD)mice,a model of human type 1 diabetes,exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient(Tlr7^(+/+))NOD *** investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin ***,Tlr7^(−/−)NOD B cells were found to suppress diabetogenic CD4^(+)T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T *** addition,we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8^(+)T-cell activation by downregulating the expression of both nonclassical and classical MHC class I(MHC-I)molecules on B *** data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T ***,therapeutically targeting TLR7 may prove beneficial for disease protection.