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 TITLE=Tim-3 Relieves Experimental Autoimmune Encephalomyelitis by Suppressing MHC-II JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.770402 DOI=10.3389/fimmu.2021.770402 ISSN=1664-3224 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.