华盛顿大学医学院Brian T. Edelson团队最新研究表明Bhlhe40介导体内稳态及2型免疫中巨噬细胞增殖的组织特异性控制。该研究成果发表于2019年6月的国际知名学术期刊《Nature Immunology》上。

该研究团队发现在大量腹膜巨噬细胞(LPMs)而非组织驻留型巨噬细胞进行自我更新和维持的过程中，转录因子Bhlhe40是其细胞内在作用方式所必需的。Bhlhe40响应细胞因子IL-4的作用，对LMPs的增殖（而非极化）是必不可少的。在感染贝克环多回卷虫属蠕虫时，LMPs的细胞周期需要Bhlhe40。Bhlhe40抑制编码转录因子c-Maf和Mafb基因的表达，并直接促进编码细胞周期相关蛋白的转录本的表达以促使LPMs增殖。在LPMs中，Bhlhe40与巨噬细胞谱系决定因子PU.1共同结合的基因组位点结合，并与包括Maf及编码细胞周期相关蛋白的基因座在内的唯一性位点结合。此研究成果证明了一种在体内稳态和2型免疫中调节驻留型巨噬细胞增殖的组织特异性调控机制。

研究表明，大多数组织驻留型巨噬细胞群在胚胎发生发育过程中产生，在稳定状态下自我更新并在2型免疫期间扩增。在体内稳态和疾病中是否有共享机制调节巨噬细胞增殖尚不清楚。

附：英文原文

Title: Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity

Author: Nicholas N. Jarjour, Elizabeth A. Schwarzkopf, Tara R. Bradstreet, Irina Shchukina, Chih-Chung Lin, Stanley Ching-Cheng Huang, Chin-Wen Lai, Melissa E. Cook, Reshma Taneja, Thaddeus S. Stappenbeck, Gwendalyn J. Randolph, Maxim N. Artyomov, Joseph F. Urban, Brian T. Edelson

Issue&Volume: Volume 20 Issue 6, June 2019

Abstract: Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state and expand during type 2 immunity. Whether shared mechanisms regulate the proliferation of macrophages in homeostasis and disease is unclear. Here we found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages (LPMs), but not that of other tissue-resident macrophages. Bhlhe40 was necessary for the proliferation, but not the polarization, of LPMs in response to the cytokine IL-4. During infection with the helminth Heligmosomoides polygyrus bakeri, Bhlhe40 was required for cell cycling of LPMs. Bhlhe40 repressed the expression of genes encoding the transcription factors c-Maf and Mafb and directly promoted expression of transcripts encoding cell cycle-related proteins to enable the proliferation of LPMs. In LPMs, Bhlhe40 bound to genomic sites co-bound by the macrophage lineage-determining factor PU.1 and to unique sites, including Maf and loci encoding cell-cycle-related proteins. Our findings demonstrate a tissue-specific control mechanism that regulates the proliferation of resident macrophages in homeostasis and type 2 immunity.

DOI: 10.1038/s41590-019-0382-5

Source:https://www.nature.com/articles/s41590-019-0382-5