<b>Gut microbiota butyrate mediated RUNX3 promotes Nr4a1</b>^<b>high</b><b>ZFP36</b>^<b>high</b> <b>resident macrophages via NR4A1/ERK1/2 MAPK to maintain gut homeostasis</b>.

ABSTRACT: Gut homeostasis is critical for systemic health, and its disruption is implicated in various diseases, including metabolic disorders. Gut-resident macrophages play a pivotal role in maintaining intestinal homeostasis, yet the mechanisms underlying their differentiation and function remain incompletely understood. Using single-cell RNA sequencing (scRNA-seq), we found a key regulatory axis in which gut microbiota-derived butyrate induces the differentiation of Nr4a1^highZFP36^high resident macrophages via RUNX3 to sustain gut homeostasis. Butyrate could upregulate RUNX3 expression in gut-resident macrophages through lncRNA lncLy6c-mediated H3K4me3 modification. Genetic ablation of RUNX3 in myeloid cells of RUNX3^{fl/fl-Lyz2-Cre} mice led to a marked

SUBMITTER: Gao Y 

PROVIDER: S-EPMC12536639 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature