ITGAE

The ITGAE gene encodes integrin alpha E, also designated CD103, a transmembrane glycoprotein that heterodimerizes with integrin β7 to form the αEβ7 complex. Primarily expressed on intraepithelial lymphocytes (IELs) and regulatory T cells (Tregs), this integrin mediates cell adhesion by binding E-cadherin on epithelial cells, facilitating immune surveillance and retention in mucosal tissues. It engages TGF-β signaling to maintain IEL populations and modulate immune tolerance. The αEβ7 integrin intersects with pathways involving PI3K/AKT and MAPK, influencing cell survival, differentiation, and inflammatory responses. Its dysfunction is implicated in inflammatory bowel disease (IBD), celiac disease, and tumor immune evasion, where altered CD103+ lymphocyte infiltration correlates with disease progression or therapeutic resistance.
CD103 has emerged as a biomarker for tissue-resident memory T cells, with prognostic value in cancers such as colorectal carcinoma and melanoma. Therapeutic strategies targeting αEβ7 aim to either enhance antitumor immunity or suppress autoimmune activity. Monoclonal antibodies like etigilimab (MTI-101) have shown preclinical efficacy in blocking Treg migration to inflamed gut mucosa. Conversely, agonists promoting CD103+ T cell retention are under evaluation in combination with PD-1 inhibitors. A phase I/II trial (NCT04128423) is assessing an αEβ7-targeting antibody-drug conjugate for solid tumors, highlighting its dual role as a therapeutic target and predictive marker in immuno-oncology.