T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules. B7 family members play a crucial role in regulating immune responses. In this study, we identified erythroid membrane-associated protein (ERMAP) as a novel T cell inhibitory molecule. ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain. The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells (APCs) and in some tumor tissues. The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages. Both mouse and human ERMAP-IgG2a Fc (ERMAP-Ig) fusion proteins inhibit T cell functions in vitro. Administration of ERMAP-Ig protein ameliorates autoimmune diseases, including experimental autoimmune encephalomyelitis and type 1 diabetes, in mice. Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro. Furthermore, administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages. Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.

T 细胞的激活和耐受性受到共刺激和共抑制分子的严格调节。 B7 家族成员在调节免疫反应中发挥着至关重要的作用。在这项研究中，我们发现红细胞膜相关蛋白（ERMAP）是一种新型 T 细胞抑制分子。 ERMAP 与其胞外域中现有的 B7 家族成员具有显着的序列和结构同源性。 ERMAP 蛋白在静息和激活的抗原呈递细胞 (APC) 的细胞表面以及某些肿瘤组织中表达。假定的 ERMAP 受体在活化的 CD4 和 CD8 T 细胞和巨噬细胞上表达。小鼠和人 ERMAP-IgG2a Fc (ERMAP-Ig) 融合蛋白均在体外抑制 T 细胞功能。给予小鼠 ERMAP-Ig 蛋白可改善自身免疫性疾病，包括实验性自身免疫性脑脊髓炎和 1 型糖尿病。抗 ERMAP 抗体在体外增强巨噬细胞对癌细胞的吞噬作用。此外，施用抗 ERMAP 抗体可能通过阻断 ERMAP 对 T 细胞和巨噬细胞的抑制作用来抑制小鼠肿瘤生长。我们的结果表明，与 ERMAP 抑制途径的治疗相互作用可能代表治疗自身免疫性疾病或癌症患者的新策略。