Novel functional roles for JAML and CAR in epithelial γδ T cell-specific costimulation (135.68)

Abstract

Abstract γδ T cells represent a major T cell population in epithelial tissues and provide a crucial first line defence against epithelial insults, yet the molecular events surrounding their activation remain poorly defined. Here we identify a γδ T cell-specific costimulatory molecule, Junctional Adhesion Molecule-Like protein (JAML). Costimulation through JAML leads to cellular proliferation, cytokine and growth factor production. Inhibition of JAML costimulation leads to diminished γδ T cell activation and delayed wound closure akin to that seen in the absence of γδ T cells. Our results identify JAML as a crucial component of epithelial γδ T cell activation. Furthermore, we show that interaction between JAML and its ligand, Coxsackie and Adenovirus receptor (CAR), extends beyond pure cell adhesion, demonstrating an important role for CAR as a signaling receptor for the immune system. This has broader implications for its proposed role in tumor migration and growth.