The conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs) originate from the same common dendritic cell precursor cells in the bone marrow. The pDCs produce large amounts of type 1 interferon in response to foreign nucleic acid and crucially contribute to host defense against viral infection. Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a pivotal component of various TNF receptor signaling pathways in the immune system. Although the functions of TRAF5 in T and B lymphocytes have been well studied, its roles in pDCs remains to be fully elucidated. In this study, we show that the expression of TRAF5 supports the generation of pDCs in the bone marrow and also critically contributes to the homeostasis of the pDC subset in the periphery in a cell-intrinsic manner. Furthermore, we provide evidence that TRAF5 promotes the commitment of DC precursor cells toward pDC versus cDC subsets, which is regulated by the balance of transcription factors TCF4 and ID2. Together our findings reveal that TRAF5 acts as a positive regulator of pDC differentiation from bone marrow progenitors. (C) 2019 Elsevier Inc. All rights reserved.