Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming.

ABSTRACT: Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 promoting a tissue-repair homeostatic state (M2_IL4). Glucocorticoids (GC), widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2_GC), but how such disparate pathways may functionally converge is unknown. We show using integrative functional genomics that M2_IL4 and M2_GC transcriptomes share a striking overlap mirrored by a shift in chromatin landscape in both common and signal-specific gene subsets. This core homeostatic program is enacted by transcriptional effectors KLF4 and the glucocorticoid receptor, whose genome-wide occupancy and actions are integrated in a stimulus-specific manner by the nuclear recepto

SUBMITTER: Deochand DK 

PROVIDER: S-EPMC11489752 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature