TRAF5 promotes plasmacytoid dendritic cell development from bone marrow progenitors

Biochem Biophys Res Commun. 2020 Jan 8;521(2):353-359. doi: 10.1016/j.bbrc.2019.10.123. Epub 2019 Oct 24.

Abstract

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.

Keywords: Cell commitment; Plasmacytoid DC; TRAF5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow
  • Bone Marrow Cells / cytology*
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Humans
  • Inhibitor of Differentiation Protein 2 / physiology
  • Stem Cells / cytology*
  • TNF Receptor-Associated Factor 5 / physiology*
  • Transcription Factor 4 / physiology
  • Transcription Factors / physiology

Substances

  • ID2 protein, human
  • Inhibitor of Differentiation Protein 2
  • TCF4 protein, human
  • TNF Receptor-Associated Factor 5
  • TRAF5 protein, human
  • Transcription Factor 4
  • Transcription Factors