上海交通大学医学院Florent Ginhoux团队的一项最新研究认为转录因子TCF4和KLF4分别控制DC2A和DC2B谱系的发育。相关论文发表在2025年7月23日出版的《自然—免疫学》杂志上。

通过结合单细胞测序、转录因子命运定位模型、条件敲除模型和过继转移，该团队发现Klf4表达清楚地区分了cDC谱系和pDC谱系，并定义了两个pre-DC2亚群：Siglec-H⁺CD115^- pre-DC2s和Siglec-H^loCD115⁺ pre-DC2s。虽然Siglec-H⁺CD115^- pre-DC2s代表以TCF4依赖性方式产生CD7⁺CD11b^lo DC2As的pDC样细胞，Siglec-H^loCD115⁺ pre-DC2s产生CD7^-CD11b^hi DC2Bs以klf4依赖的方式。这些数据揭示了两个前DC2亚群的转录基础，并为小鼠cDC分类提供了一个坚实的框架，为更好地了解组织和疾病中的这些细胞铺平了道路。

研究人员表示，传统的树突状细胞（cDC）是一种异质的专业抗原呈递细胞，架起先天免疫和适应性免疫的桥梁。在小鼠中进行的许多研究已经确定了各种各样的cDC群体，它们的相互关系和离散身份，以及它们与浆细胞样DCs（pDCs）的联系，尚未得到完整的解决。

附：英文原文

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

Author: Zhu, Yiwen, Cai, Peiliang, Li, Ziyi, Zhang, Shuangyan, Kong, Wan Ting, Wang, Haiting, Gao, Fei, Zeng, Yingying, Qian, Jiawen, Su, Bing, Liu, Zhaoyuan, Ginhoux, Florent

Issue&Volume: 2025-07-23

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 CD7CD11bhi 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.

DOI: 10.1038/s41590-025-02208-5

Source: https://www.nature.com/articles/s41590-025-02208-5