Lymphoid origin of intrinsically activated plasmacytoid dendritic cells in mice

Elife. 2024 Sep 13:13:RP96394. doi: 10.7554/eLife.96394.

Abstract

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a. These CLP-derived pDCs, which we refer to as 'B-pDCs', have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL+ transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice.

Keywords: B cells; CLPs; immunology; inflammation; mouse; plasmacytoid DCs.

MeSH terms

  • Animals
  • Cell Lineage
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Gene Expression Profiling
  • Lymphocyte Activation
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Associated data

  • GEO/GSE105827
  • GEO/GSE99019
  • GEO/GSE225768
  • GEO/GSE52868