CD300e Acts As A Ligand To Inhibit T Cell Immunity

Abstract CD300e has been reported as either an activating or inhibitory receptor and is involved in the tuning of immune responses. In this study, we demonstrate that CD300e acts as a ligand through an unknown receptor to inhibit T cell immunity. In PBMCs, CD300e protein is expressed on the cell surface of CD14+ monocytes, but not on T and B cells. CD300e-Fc fusion protein significantly reduced the expression of CD69 and CD25 on T cells, which suggest that CD300e inhibits the activation of T cells. Furthermore, CD300e-Fc fusion protein significantly inhibited TCR-mediated T cell proliferation and cytokine production including IL-2, IFN-gamma, IL-17, TNF-alpha, IL-8 and IP-10/CXCL10. Florescent conjugated CD300e-Fc fusion protein significantly bound to activated T cells and weakly to inactive T cells, suggesting that the putative CD300e counter-receptor is expressed on the cell surface of T cells, and the expression levels are upregulated upon T cell activation. CD300e-Fc fusion protein inhibited TCR-mediated p38 MAPK phosphorylation which indicates that CD300e negatively regulates T cell activation by impairing the p38 MAPK dependent antigen presentation. Moreover, our results support the notion that CD300e might be a new player in the regulation of the expansion of T cell-mediated responses. This CD300e novel T cell inhibitory pathway may provide a new strategy to modulate T cell-mediated immunity to treat immune-related diseases.