Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization.

Dendritic cells (DCs) are professional antigen presenting cells that activate and modulate immune responses, but the mechanisms underlying DC activation have not been fully understood. In this study, we investigated the role of Notch signaling in DC activation by using murine bone marrow-derived DCs. Triggering of Toll-like receptors (TLRs) of DCs led to upregulated expression of Notch ligands. Disruption of Notch signaling by the deletion of RBP-J, the critical transcription factor mediating the canonical signaling from all Notch receptors, resulted in a reduced capacity of DCs in activating T cells. Moreover, RBP-J deficiency altered the polarization of T cell activation, as manifested by downregulated interferon-γ and upregulated interleukin-4 and -10 expressions after LPS or Poly(I:C) stimulation. Furthermore, we found that RBP-J(-/-) DCs had reduced intracellular calcium after TLR-triggering. Immunofluorescent staining showed that RBP-J deficient DCs exhibited attenuated cytoskeleton reorganization when contacting T cells. In summary, our results suggested that the canonical Notch signaling promotes the cytoskeleton reorganization and the TLR-mediated DC activation.