Integrin α4β7: Pathogenic Roles in Metabolic and Inflammatory Diseases and Translational Therapeutics.

Integrin α4β7 is a key adhesion receptor that mediates lymphocyte homing to the intestinal mucosa through interactions with MAdCAM-1, VCAM-1, and fibronectin, thereby playing a central role in gut immune surveillance and mucosal immunity. Emerging evidence has expanded its functional scope beyond intestinal homeostasis to encompass diverse inflammatory and metabolic diseases. This review systematically summarizes the structural characteristics, ligand interactions, and conformational regulation of α4β7, with an emphasis on its pathogenic roles in inflammatory bowel disease, cardiovascular diseases, diabetes, liver disorders, autoimmune diseases, gastrointestinal malignancies, HIV infection, asthma, and graft-versus-host disease. We discuss the underlying mechanisms, including lymphocyte trafficking, T cell co-stimulation, immune subset dysregulation, and crosstalk with the gut microbiota and epithelial barrier. In addition, we review the current landscape of α4β7-targeting therapeutics, including vedolizumab, etrolizumab, ontamalimab, and small-molecule antagonists, highlighting their clinical applications and limitations. By integrating recent mechanistic insights and therapeutic advances, this review provides a comprehensive framework for understanding the multifaceted roles of α4β7 and informs future strategies for targeting this integrin in disease.