Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells

Nat Immunol. 2023 Apr;24(4):714-728. doi: 10.1038/s41590-023-01454-9. Epub 2023 Mar 16.

Abstract

Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN- pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells*
  • Gene Expression Profiling
  • Interferon Type I* / metabolism
  • Mice
  • Phenotype
  • Transcriptome

Substances

  • Interferon Type I