Gao Yunhuan, Zhou Jiang, Qi Houbao, Wei Jianmei, Yang Yazheng, Yue Jianmei, Liu Xinqi, Zhang Yuan, Yang Rongcun
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin 300071, China.
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
Cell Discov. 2020 Nov 24;6(1):87. doi: 10.1038/s41421-020-00211-8.
Macrophages are mainly divided into two populations, which play a different role in physiological and pathological conditions. The differentiation of these cells may be regulated by transcription factors. However, it is unclear how to modulate these transcription factors to affect differentiation of these cells. Here, we found that lncLy6C, a novel ultraconserved lncRNA, promotes differentiation of Ly6C inflammatory monocytes into Ly6C resident macrophages. We demonstrate that gut microbiota metabolites butyrate upregulates the expression of lncLy6C. LncLy6C deficient mice had markedly increased Ly6C pro-inflammatory monocytes and reduced Ly6C resident macrophages. LncLy6C not only bound with transcription factor C/EBPβ but also bound with multiple lysine methyltransferases of H3K4me3 to specifically promote the enrichment of C/EBPβ and H3K4me3 marks on the promoter region of Nr4A1, which can promote Ly6C into Ly6C macrophages. As a result, lncLy6C causes the upregulation of Nr4A1 to promote Ly6C inflammatory monocytes to differentiate into Ly6C resident macrophages.
巨噬细胞主要分为两类，它们在生理和病理条件下发挥着不同的作用。这些细胞的分化可能受转录因子调控。然而，目前尚不清楚如何调节这些转录因子来影响这些细胞的分化。在此，我们发现lncLy6C，一种新型的超保守长链非编码RNA，可促进Ly6C炎性单核细胞分化为Ly6C驻留巨噬细胞。我们证明肠道微生物群代谢产物丁酸可上调lncLy6C的表达。lncLy6C缺陷小鼠的Ly6C促炎单核细胞显著增加，而Ly6C驻留巨噬细胞减少。lncLy6C不仅与转录因子C/EBPβ结合，还与多种H3K4me3赖氨酸甲基转移酶结合，特异性促进C/EBPβ和H3K4me3标记在Nr4A1启动子区域的富集，从而促进Ly6C转变为Ly6C巨噬细胞。因此，lncLy6C导致Nr4A1上调，促进Ly6C炎性单核细胞分化为Ly6C驻留巨噬细胞。
