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Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of human MS. Erythrocyte membrane\u2010associated protein (ERMAP) is a novel erythrocyte\u2010specific adhesion\/receptor molecule associated with erythrocyte adhesion. We have previously characterised it as a novel inhibitory immune checkpoint molecule and demonstrated that recombinant ERMAP proteins ameliorate EAE; however, the specific mechanism of action of ERMAP and the effects of endogenous ERMAP on T\u2010cell function are largely unknown. In this study, we investigate the role of endogenous ERMAP in T\u2010cell and macrophage homeostasis and EAE development. We show here that erythrocyte membrane\u2010associated protein (ERMAP) gene knockout (ERMAP<jats:sup>\u2212\/\u2212<\/jats:sup>) mice have increased numbers of T cells and pro\u2010inflammatory M1 macrophages and enhanced T\u2010cell activation, as compared to wild\u2010type (ERMAP<jats:sup>+\/+<\/jats:sup>) mice. When induced to develop EAE, ERMAP<jats:sup>\u2212\/\u2212<\/jats:sup> mice have more severe EAE symptoms and pathology, which are related to increased numbers of T cells (especially Th1 and Th17 T cells) and M1 macrophages, enhanced activation of T cells, and increased generation of inflammatory cytokines, but decreased proportion of Th2 T cells, regulatory T cells (Tregs), and anti\u2010inflammatory M2 macrophages. Global gene analysis by RNA\u2010seq shows that signalling molecules in the peroxisome proliferator\u2010activated receptor (PPAR) pathway are decreased in ERMAP<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Our results suggest that endogenous ERMAP plays an important role in T\u2010cell and macrophage homeostasis and EAE development.<\/jats:p>","DOI":"10.1111\/imm.13910","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:00:48Z","timestamp":1741694448000},"page":"200-213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endogenous <scp>ERMAP<\/scp> Affects T\u2010Cell Function in <scp>EAE<\/scp> Mice"],"prefix":"10.1111","volume":"175","author":[{"given":"Keke","family":"He","sequence":"first","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Histology and Embryology Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kezhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Histology and 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