CD99 regulates CD1A expression during dendritic cells differentiation (147.14)

Abstract

Abstract Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a dominant role in the regulation of immune responses. CD1a has a unique expression pattern among Ag-presenting molecules, expressed specifically on cortical thymocytes and APCs. We have previously established that CD99, a 32kd transmembrane molecule expressed as two isoforms, could regulate classical MHC class I expression. We found that CD99LF triggers phosphorylation of p38 mitogen-activated protein kinase (MAPK) and two activating transcription factor (ATF)/CREB family members, CREB-1 and ATF-2 to inhibit CD1a expression in DC derived from monocytes CD14+. We also showed that this regulation is counteracted in the presence of CD99 short form (CD99SF).To confirm our results, we used CD99 deficient Jurkat cells and CD99pos transfected cells, CD99 silencing experiments and inhibitors/activators of cell-signaling pathways. Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1a expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. This study strongly suggests a role for CD99 in regulation of differentiation of DCs subtype. In conclusion, we propose that cAMP is a novel pathway exploited by CD99 to regulate CD1a expression.