RRC ID 85362
Author Zhu Y, Cai P, Li Z, Zhang S, Kong WT, Wang H, Gao F, Zeng Y, Qian J, Su B, Liu Z, Ginhoux F.
Title Transcription factors TCF4 and KLF4 respectively control the development of the DC2A and DC2B lineages.
Journal Nat Immunol
Abstract Conventional dendritic cells (cDCs) are a heterogeneous population of professional antigen-presenting cells that bridge innate and adaptive immunity. Many studies in mice have identified various populations of cDCs whose inter-relationships and discrete identities, as well as their link to plasmacytoid DCs (pDCs), have not been cohesively addressed. Here, by combining single-cell sequencing, transcription factor fate-mapping models, conditional knockout models and adoptive transfer, we show that Klf4 expression clearly separates cDC lineage from the pDC lineage, and defined two pre-DC2 subsets: Siglec-H+CD115- pre-DC2s and Siglec-HloCD115+ pre-DC2s. While Siglec-H+CD115- pre-DC2s represent the pDC-like cells that give rise to CD7+CD11blo DC2As in a TCF4-dependent manner, Siglec-HloCD115+ pre-DC2s give rise to CD7-CD11bhi DC2Bs in a KLF4-dependent manner. These data reveal the transcriptional basis of two pre-DC2 subsets and present a firm framework for mouse cDC classification, paving the way for a better understanding of these cells in tissues and in disease.
Published 2025-7-23
DOI 10.1038/s41590-025-02208-5
PII 10.1038/s41590-025-02208-5
PMID 40702338
IF 20.479
Resource
Mice RBRC02704