eLife (Sep 2024)

Lymphoid origin of intrinsically activated plasmacytoid dendritic cells in mice

  • Alessandra Machado Araujo,
  • Joseph D Dekker,
  • Kendra Garrison,
  • Zhe Su,
  • Catherine Rhee,
  • Zicheng Hu,
  • Bum-Kyu Lee,
  • Daniel Osorio,
  • Jiwon Lee,
  • Vishwanath R Iyer,
  • Lauren IR Ehrlich,
  • George Georgiou,
  • Gregory Ippolito,
  • Stephen Yi,
  • Haley O Tucker

DOI
https://doi.org/10.7554/eLife.96394
Journal volume & issue
Vol. 13

Abstract

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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.

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