A novel adaptor protein, ARAP, orchestrates Fcγ receptor signaling in mouse dendritic cells via Rap1 activation and NF-κB-mediated cytokine production.

Fcγ receptors (FcγRs), key mediators of antibody-dependent immune responses, are critical for dendritic cell (DC) activation and adaptive immunity initiation. Although the general importance of FcγR signaling is well established, the specific intracellular pathways remain insufficiently defined. ARAP (activation-dependent, raft-recruited ADAP-like phosphoprotein) is a novel adaptor protein identified in T-cell receptor signaling pathways. ARAP is expressed across various tissues and cell types, including DCs. To address the functional significance of ARAP, homologous recombination was performed to generate mice with an ARAP deficiency. In this study, we investigated the role of ARAP in FcγR-mediated DC function using ARAP-deficient mice. The results revealed that bone marrow-derived DCs from ARAP-deficient mice exhibited defects in FcγR-mediated proximal signaling and integrin-mediated adhesion. In addition, ARAP-deficient DCs exhibited reduced nuclear translocation of NF-κB p65 and decreased production of inflammatory cytokines. These findings establish ARAP as a selective and critical regulator of FcγR signaling, suggesting FcγR involvement in dendritic cell Rap1-mediated adhesion and NF-κB-dependent cytokine responses.