The junctional adhesion molecule-like protein (JAML) is important for the inflammatory response during contact hypersensitivity

Background: The junctional adhesion molecule-like protein (JAML) plays important roles in wound healing and activation of epidermal gamma delta T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known.Methods: To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild-type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo.Results: JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8+ and CD4+ T cells in the epidermis. Furthermore, interferon gamma (IFN gamma), interleukin 1 beta (IL-1 beta) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8(+) T cells express JAML and that JAML is essential for rapid flare-up responses to contact allergens. Finally, we show that keratinocytes up-regulate the JAML ligand CXADR following exposure to contact allergens.Conclusion: Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans.