Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells

作     者：Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S.Westerberg Chaohong Liu 

作者机构：Department of Pathogen BiologyTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China Department of ImmunologySchool of MedicineYangtze UniversityJingzhouHubei Province434023PR China Department of EndocrinologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China The Second Department of PediatricsAffiliated Hospital of Zunyi Medical UniversityZunyiGuiZhou Province563000PR China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm17177Sweden 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2021年第8卷第3期

页      面：344-352页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：supported by National NaturalScience Foundation of China(grant numbers 81861138002 81722002 31970839 31900654)。 

主　　题：CD25 Foxp3 ICOS Regulator T cell USP18 

摘      要：Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory T(Treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of USP18 on the impact of Treg cell differentiation and function.We found that USP18 deficiency upregulates the differentiation of Treg cells,which may lead to disrupted homeostasis of peripheral T cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)T cells and INF-γproducing CD8^(+)T cells.Mechanistically,we also found that the upre-gulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO Tregs is downregulated.Altogether,our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function,which may provide a new reference for the treatment of Treg function in many autoimmune diseases,and USP18 can be used as a new therapeutic target for precise medical treatment.