From inflammatory effectors to tissue sculptors: non-canonical functions of neutrophils in repair, barrier remodelling and fibrosis.

Traditionally, neutrophils have been viewed as short-lived effector cells of acute inflammation, specialized for chemotaxis, phagocytosis, degranulation, reactive oxygen species production and neutrophil extracellular trap formation. This view remains central to host defence, but emerging evidence indicates that, in defined tissue and disease contexts, neutrophils can also regulate tissue architecture. In this review, we explain how canonical neutrophil effector mechanisms acquire structural consequences, focusing on neutrophil-matrix interactions during wound repair, barrier remodelling and disease-conditioned neutrophil states in organ fibrosis. Neutrophils can influence extracellular matrix degradation, matrix transport, local matrix organisation, barrier stability and stromal inflammatory responses; these activities may support early repair, but when persistent or dysregulated, they may contribute to a pro-fibrotic niche by amplifying inflammation, modifying matrix architecture and licensing fibroblast activation. The central conceptual advance is that neutrophils should be understood not as primary fibrogenic cells, but as transient, context-dependent structural regulators that can initiate, modify or amplify tissue remodelling according to timing, tissue niche and inflammatory persistence. Because much of the mechanistic evidence derives from mouse models, we also discuss human translation and the need to selectively restrain maladaptive neutrophil programmes without compromising host defence or early repair.