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-ass...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.展开更多
基金This work was supported by grants from the NIH(1R01AI123131–01)the Connecticut Regenerative Medicine Research Fund(16-RMB-UCONN-02).
文摘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.
