The regulatory logic linking inflammation and fibrosis.

Abstract

Whether tissue injury resolves or progresses to chronic scarring is determined by regulatory choices that remain only partially understood. In this review, we propose that immune cells and fibroblasts function as dynamic interpreters of intercellular cues, integrating these signals through chromatin-regulated gene circuits that govern cell state and fate. Drawing on insights from cardiac biology and from settings where tissues regenerate or resolve injury without scarring, we outline a molecular framework in which immune-stromal crosstalk and gene regulatory networks dictate the choice between recovery and chronic fibrosis across organs, including the heart, lung, liver, and kidney. Reframing fibrosis as a reversible state shaped by disrupted regulatory logic opens therapeutic avenues that move beyond suppressing fibrotic outputs toward rewiring the regulatory programs that sustain them.