ITGAE (integrin subunit alpha E), also known as CD103, encodes the alpha-E subunit of the αE/β7 integrin heterodimer, a specialized adhesion receptor that mediates epithelial cell recognition and lymphocyte tissue residency. The protein functions as a receptor for E-cadherin, enabling firm adhesion of intraepithelial T lymphocytes to epithelial cell monolayers and facilitating their retention within tissues 1. Mechanistically, ITGAE expression defines tissue-resident memory (Trm) T cells across multiple barrier tissues. CD8+ and CD4+ Trm cells express elevated ITGAE alongside other tissue-residency markers (CXCR6, CD69), establishing their commitment to local immune surveillance 1. In intestinal Crohn's disease, Th17 Trm cells demonstrate heightened ITGAE expression correlated with increased IL-17A and IL-22 production, promoting transmural inflammation 2. ITGAE+ CD8 T cells also appear in tumor microenvironments: CXCL13+ CD8-PreTex cells expressing ITGAE show higher cytotoxicity and lower exhaustion in intrahepatic cholangiocarcinoma 3, while EBV+ gastric cancers display elevated ITGAE expression associated with superior immune infiltration and anti-PD-1 responsiveness 4. Clinically, ITGAE represents a potential therapeutic target. In primary Sjögren's syndrome, intraglandular anti-CD103 blockade reduced Trm cell accumulation, mitigated glandular damage, and improved salivary flow 5. In checkpoint inhibitor colitis, ITGAE-high CD8 tissue-resident memory T cells expressing CXCL13 and Th17 programs expand pathologically 6. These findings suggest ITGAE-targeted interventions may modulate tissue-damaging inflammation while potentially enhancing anti-tumor immunity in immunotherapy-responsive malignancies.