The Roles of Neutrophil Cells in the Pathogenesis of Fibrosis: Mechanisms for Disease Progression.

Fibrosis is a dysregulated tissue repair process with dynamic reorganization of extracellular matrix. Neutrophils have traditionally been viewed as short-lived, first-responder immune cells primarily involved in acute inflammation and pathogen clearance. However, accumulating evidence reveals that they also play multifaceted roles in the pathogenesis of fibrosis across multiple organs. Through the release of cytokines, granule proteins, neutrophil extracellular traps, and metabolic mediators, as well as through interactions with fibroblasts, macrophages, and other immune cells, neutrophils actively shape the fibrotic microenvironment and influence disease progression. Importantly, neutrophils exhibit both pro- and antifibrotic functions, depending on their activation state, local cues, and disease context. The review aims to summarize the cellular mechanisms of neutrophils involved in the fibrotic process and various tissues, including the lung, liver, kidneys, and heart. We aim to deepen our understanding of the complex relationship between neutrophils and fibrosis and to offer new perspectives for the development of neutrophil-targeted immunomodulatory therapies for fibrotic diseases.