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

Abstract

Summary Costimulation through Junctional Adhesion Molecule-Like protein interaction with Coxsackie and Adenovirus Receptor mediates epithelial γδ T cell-specific activation and effector function during tissue repair. γδ T cells present in epithelial tissues provide a crucial first line of defence against environmental insults, including infection, trauma and malignancy, yet the molecular events surrounding their activation remain poorly defined. Here we identify an epithelial γδ 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 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 biology and have broader implications for CAR and JAML in tissue homeostasis and repair.

JAML mediates monocyte and CD8 T cell migration across the brain endothelium

“…Interestingly, monocyte adhesion to the endothelium also induced the formation of transmigratory cups enriched in p120, providing further evidence for the expression of junctional proteins by leukocytes11 and emphasizing the role of p120 as an intracellular mediator of monocyte migration 12. In addition, JAML expression on myeloid and CD8 T cells populations within the CNS is an important aspect that warrants further investigation as JAML is also a costimulatory molecule able to support cell activation and effector functions 13. The migration of neutrophils and monocytes across epithelium and EC lines was shown to be decreased when JAML is blocked 4, 14.…”

Neutrophil-Epithelial Interactions

“…82 These results appear at odds with other reports of JAML-CAR interactions facilitating T-cellemediated wound healing in the skin of mice. 83 However, in those studies, prorestitutive signals were derived downstream of from T-cell expressed JAML, whereas the inhibitory signals during transepithelial migration of neutrophils were derived downstream of epithelial expressed CAR. These observations suggest that bidirectional signals emanating from JAML-CAR interactions mediate complex effects on epithelial function through direct and indirect mechanisms.…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…67 In addition to the conventional costimulators that are shared with ab-T cells, several novel molecules can serve as the secondary signals for the activation of cd-T cells. It has been found that the expression of junctional adhesion molecule-like protein 68 and high-mobility group box 1 69 by cd-T cells provides positive signals for the activation of cd-T cells, whereas stimulation with E-cadherin downregulates their functions. 70 The natural killer (NK) cell receptor family is another important group of costimulators for regulating the activity of cd-T cells, and the balance among stimulatory and inhibitory natural killer WW (NK) cell receptor signals might determine the functions of cd-T cells.…”