The eNAMPT-Integrin α5β1 Axis Mediates Neutrophil-Endothelial Cell Interactions Driving Inflammation in Ulcerative Colitis.

BACKGROUND

Ulcerative colitis (UC), a chronic inflammatory bowel disease with rising global incidence, involves neutrophil-driven mucosal damage. The precise mechanisms remain elusive, hindering targeted therapies. Therefore, this study aims to integrate single-cell transcriptomics with in vivo experiments to reveal the key signaling axes driving pathogenic neutrophil activation in UC.

METHODS

Single-cell transcriptomics characterized UC inflammatory microenvironments, focusing on neutrophil functional states and intercellular interactions. Based on key findings from bioinformatics analysis, we hypothesize that the eNAMPT-integrin α5β1 signaling axis drives abnormal neutrophil-endothelial cell communication and functionally validate this hypothesis in in vivo models.

RESULTS

Neutrophils exhibited aberrant activation and significant NAMPT overexpression in UC. Extracellular eNAMPT functioned as a signaling molecule binding endothelial integrin α5β1, mediating pathological neutrophil-endothelial crosstalk. Pharmacological blockade of the eNAMPT/integrin α5β1 axis inhibited neutrophil mucosal infiltration, reducing inflammation and tissue damage in UC mouse models.

CONCLUSION

The eNAMPT-integrin α5β1-mediated neutrophil-endothelial communication axis represents a novel pathogenic pathway in UC, providing a foundation for precision therapies targeting this mechanism.