biostudies-literatureDeochand DKNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)The Hospital for Special Surgery David Rosensweig Genomics CenterU.S. Department of Health & Human Services | National Institutes of Health9000https://www.ebi.ac.uk/biostudies/studies/S-EPMC11489752biostudies-literatureUnknown15(1)Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 promoting a tissue-repair homeostatic state (M2<sub>IL4</sub>). Glucocorticoids (GC), widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2<sub>GC</sub>), but how such disparate pathways may functionally converge is unknown. We show using integrative functional genomics that M2<sub>IL4</sub> and M2<sub>GC</sub> 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 receptoNature communicationsMechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming.PMC11489752NIH R01AI148416F31 HL152706F31 HL152706-01A1R01 AI148129R01 AI148416NIH R01AI148129NIH R01DK099087R01 DK099087Deochand DKOliver DBale MJChinenov YChaudhary VRogatsky IJosefowicz SZDacic MDaman AWfalseMechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming.Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 promoting a tissue-repair homeostatic state (M2<sub>IL4</sub>). Glucocorticoids (GC), widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2<sub>GC</sub>), but how such disparate pathways may functionally converge is unknown. We show using integrative functional genomics that M2<sub>IL4</sub> and M2<sub>GC</sub> 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 recepto2024-01-01T00:00:00Z2024 Oct2026-07-15T04:58:36.812Z2025-04-04T01:46:45.888ZS-EPMC114897523942478010.1038/s41467-024-52942-x