Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells

Nat Immunol. 2018 Jul;19(7):711-722. doi: 10.1038/s41590-018-0136-9. Epub 2018 Jun 20.

Abstract

Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, whereas pDC identity relies on TCF4. RNA sequencing of IL-7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed in single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • Cell Lineage
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • GTPase-Activating Proteins / metabolism
  • Interferon Regulatory Factors / metabolism
  • Lectins / metabolism
  • Male
  • Mice
  • Receptors, Cell Surface / metabolism
  • Receptors, Interleukin-7 / metabolism
  • Stem Cells / immunology*
  • Trans-Activators / metabolism
  • Transcription, Genetic

Substances

  • Ebf1 protein, mouse
  • GTPase-Activating Proteins
  • Interferon Regulatory Factors
  • Lectins
  • Receptors, Cell Surface
  • Receptors, Interleukin-7
  • Siglech protein, mouse
  • TBC1D15 protein, mouse
  • Trans-Activators
  • interferon regulatory factor-8