Tim-3 Relieves Experimental Autoimmune Encephalomyelitis by Suppressing MHC-II.

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) inhibi

SUBMITTER: Tang L 

PROVIDER: S-EPMC8793033 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature