Pestal Kathleen, Slayden Leianna C, Barton Gregory M
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Howard Hughes Medical Institute, University of California, Berkeley, Berkeley CA 94720, USA.
bioRxiv. 2024 Mar 3:2024.02.28.582578. doi: 10.1101/2024.02.28.582578.
Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Kruppel-like Factor 2 (KLF2) in the development of embryonically derived Large Cavity Macrophages (LCM) in the serous cavities. KLF2 not only directly regulates the transcription of genes previously shown to specify LCM identity, such as retinoic acid receptors and GATA6, but also is required for induction of many other transcripts that define the identity of these cells. We identify a similar role for KLF4 in regulating the identity of alveolar macrophages in the lung. These data demonstrate that broadly expressed transcription factors, such as Group 2 KLFs, can play important roles in the specification of distinct identities of tissue-resident macrophages.
组织驻留巨噬细胞根据其驻留组织采用不同的基因表达谱并表现出功能特化。最近的研究已开始确定诱导这些特性的信号和转录因子。在此，我们描述了广泛表达的转录因子Kruppel样因子2（KLF2）在浆膜腔中胚胎来源的大腔巨噬细胞（LCM）发育中的一个意外且特定的作用。KLF2不仅直接调节先前已证明可确定LCM特性的基因转录，如视黄酸受体和GATA6，而且对于诱导许多其他定义这些细胞特性的转录本也是必需的。我们确定KLF4在调节肺中肺泡巨噬细胞的特性方面具有类似作用。这些数据表明，广泛表达的转录因子，如2组KLFs，可在组织驻留巨噬细胞不同特性的特化中发挥重要作用。
