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

Yongcheng Di,1,2,* Wenbin Ji,1,2,* Wenhao Xiong,1,2,* Wenbin Song,1,2 Guoshan Chen,1,2 Danzhou Li,1,2 Feng Qi1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Qi, Email [email protected]: 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 α 5β 1 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 α 5β 1, mediating pathological neutrophil-endothelial crosstalk. Pharmacological blockade of the eNAMPT/integrin α 5β 1 axis inhibited neutrophil mucosal infiltration, reducing inflammation and tissue damage in UC mouse models.Conclusion: The eNAMPT-integrin α 5β 1-mediated neutrophil-endothelial communication axis represents a novel pathogenic pathway in UC, providing a foundation for precision therapies targeting this mechanism.Keywords: ulcerative colitis, neutrophils, endothelial cells, NAMPT, bioinformatics