Impact of Neutrophils on the Tissue Microenvironment During Intestinal Inflammation

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Neutrophils (polymorphonuclear leukocytes, PMN) are key innate immune cells that accumulate at mucosal surfaces during inflammation.
• Sustained PMN activation disrupts epithelial barriers, remodels extracellular matrix, causes metabolic imbalance, and dysregulates the microbiome.
• These PMN-driven processes contribute to persistent tissue injury and treatment resistance in chronic inflammatory diseases like inflammatory bowel disease (IBD).

Purpose of the Study:

• To synthesize current evidence on how PMNs shape the inflamed mucosal microenvironment.
• To highlight mechanisms of PMN recruitment, retention, survival, and effector functions.
• To discuss PMN-driven metabolic and microbiome alterations and their impact on therapy response.

Main Methods:

• Review of human mucosal biopsies and experimental models of intestinal inflammation.
• Integration of data from single-cell, spatial, and metabolic profiling approaches.
• Analysis of bidirectional crosstalk between PMNs and other tissue compartments.

Main Results:

• PMNs are recruited, retained, and survive in inflamed mucosa, executing effector programs like ROS production and NET formation.
• PMNs engage in complex crosstalk with epithelial, stromal, and immune cells.
• PMN activity significantly impacts host metabolism and the gut microbiome, influencing inflammation chronicity and therapeutic outcomes.

Conclusions:

• PMNs act as context-dependent regulators of mucosal pathology and repair.
• PMN-centered pathways represent promising targets for precision therapies.
• Targeting PMNs can restore barrier function and promote durable inflammatory resolution in IBD and other chronic inflammatory conditions.