Work

Chromatin Remodeling and Transcriptional Silencing Define the Dynamic Innate Immune Response of Tissue Resident Macrophages After Burn Injury

Year: 2025

Type: article

Abstract: Severe burn injury induces prolonged immune dysfunction, but the underlying molecular mechanisms remain poorly defined. We hypothesized that burn injury causes epigenetic and transcriptional training of innate immune cells. Splenic F4/80⁺ macrophages were isolated from mice at 2, 9, and 14 days after 20% total body surface area contact burn. Targeted transcriptomics and chromatin profiling revealed a biphasic response: early transcriptional silencing of inflammatory genes (e.g., Stat3 , Traf6 , and Nfkb1 ), followed by increased accessibility and expression of anti-inflammatory loci ( Il-10 and Socs3 ). Metabolic genes showed persistent suppression of mitochondrial and oxidative phosphorylation programs. Canonical pathway analysis indicated early interleukin-10 signaling activation and long-term repression of classical macrophage activation. Chromatin remodeling included nucleosome repositioning events, supporting dynamic, and locus-specific regulation. These findings challenge the notion that burn-induced immune suppression is solely due to systemic inflammation and instead suggest durable, epigenetically programmed alterations in macrophage function.

Source: Shock

DOI: 10.1097/shk.0000000000002746