, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy.

is an adapter protein involved in receptor-mediated signaling, endocytosis, cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a pivotal role in controlling cellular homeostasis. In the immune system, the is a Foxp3 target gene and is required for regulatory T (Treg) cell function. expression and its biological function in dendritic cells (DCs) have not been described. In this study, we found that was significantly induced during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs). Even in a steady state, was expressed in mouse splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for expression during GM-CSF-derived BMDC development regardless of TGF-β signaling. -silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice. Vaccination with -silenced DCs inhibited tumor growth more effectively than did vaccination with wild type DCs. -overexpression abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These data strongly suggest that might be an intrinsic negative regulator of the immunogenicity of DCs, thus might be an attractive molecular target to improve DC vaccine efficacy.