Redefining Neutrophil Function in Inflammatory Bowel Disease: From Tissue Injury to Immune Resolution

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation driven by dysregulated immune responses and impaired mucosal homeostasis. Although neutrophils have traditionally been viewed as short-lived pro-inflammatory effector cells that contribute to epithelial injury, emerging evidence indicates that they also possess important pro-resolving and tissue-repairing functions. This narrative mini-review critically evaluates recent advances in understanding neutrophil functional heterogeneity in IBD, with particular emphasis on CD177⁺ neutrophils, neutrophil extracellular trap formation, efferocytosis, and mechanisms involved in immune resolution and mucosal healing. Accumulating data suggest that specialized neutrophil subsets can balance antimicrobial defense with controlled inflammatory signaling, thereby contributing to epithelial protection and restoration of intestinal homeostasis. In parallel, efficient efferocytosis of apoptotic neutrophils by macrophages emerges as a central mechanism promoting resolution of inflammation, whereas impaired clearance sustains chronic inflammatory responses. Recent studies further highlight the therapeutic potential of targeting pro-resolving neutrophil pathways and enhancing efferocytosis; however, most current evidence remains preclinical, and significant challenges persist in translating these findings into human therapies. Collectively, these insights redefine neutrophils as dynamic regulators of both tissue injury and immune resolution in IBD and support the development of therapeutic strategies aimed at restoring immune balance and durable mucosal healing.