The Junctional Adhesion Molecule JAML Is a Costimulatory Receptor for Epithelial γδ T Cell Activation

gamma delta T cells present in epithelial tissues provide a crucial first line of defense against environmental insults, including infection, trauma, and malignancy, yet the molecular events surrounding their activation remain poorly defined. Here we identify an epithelial gamma delta T cell-specific costimulatory molecule, junctional adhesion molecule-like protein (JAML). Binding of JAML to its ligand Coxsackie and adenovirus receptor (CAR) provides costimulation leading to cellular proliferation and cytokine and growth factor production. Inhibition of JAML costimulation leads to diminished gamma delta T cell activation and delayed wound closure akin to that seen in the absence of gamma delta T cells. Our results identify JAML as a crucial component of epithelial gamma delta T cell biology and have broader implications for CAR and JAML in tissue homeostasis and repair.