Author:
Tang Lili,Li Ge,Zheng Yang,Hou Chunmei,Gao Yang,Hao Ying,Gao Zhenfang,Mo Rongliang,Li Yuxiang,Shen Beifen,Wang Renxi,Wang Zhiding,Han Gencheng
Abstract
Tim-3, an immune checkpoint inhibitor, is widely expressed on the immune cells and contributes to immune tolerance. However, the mechanisms by which Tim-3 induces immune tolerance remain to be determined. Major histocompatibility complex II (MHC-II) plays a key role in antigen presentation and CD4+T cell activation. Dysregulated expressions of Tim-3 and MHC-II are associated with the pathogenesis of many autoimmune diseases including multiple sclerosis. Here we demonstrated that, by suppressing MHC-II expression in macrophages via the STAT1/CIITA pathway, Tim-3 inhibits MHC-II-mediated autoantigen presentation and CD4+T cell activation. As a result, overexpression or blockade of Tim-3 signaling in mice with experimental autoimmune encephalomyelitis (EAE) inhibited or increased MHC-II expression respectively and finally altered clinical outcomes. We thus identified a new mechanism by which Tim-3 induces immune tolerance in vivo and regulating the Tim-3-MHC-II signaling pathway is expected to provide a new solution for multiple sclerosis treatment.
Funder
National Natural Science Foundation of China
Beijing Municipal Natural Science Foundation
Subject
Immunology,Immunology and Allergy
Cited by
5 articles.
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