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. 2025 Aug;26(8):1275-1286.
doi: 10.1038/s41590-025-02208-5. Epub 2025 Jul 23.

Transcription factors TCF4 and KLF4 respectively control the development of the DC2A and DC2B lineages

Yiwen Zhu  1 , Peiliang Cai  1 , Ziyi Li  2 , Shuangyan Zhang  1 , Wan Ting Kong  3 , Haiting Wang  1 , Fei Gao  1 , Yingying Zeng  1 , Jiawen Qian  1 , Bing Su  1   4 , Zhaoyuan Liu  5   6   7 , Florent Ginhoux  8   9   10   11
Affiliations

Transcription factors TCF4 and KLF4 respectively control the development of the DC2A and DC2B lineages

Yiwen Zhu et al. Nat Immunol. 2025 Aug.

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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