337 JAML propels the inflammatory responses to contact allergens

Allergic contact dermatitis (ACD) is a skin disease with a complex pathophysiology. It is well established that epidermal-resident memory CD8+ T (CD8+ TRM) cells are responsible for the rapid flare-up reaction and production of IFNγ and IL-17A seen after challenge with contact allergens. Nevertheless, pathways that kick off their effector functions are unclear. Junctional adhesion molecule-like protein (JAML) was recently described as important in promoting effector functions of tumor-infiltrating CD8+ T cells, but its role in ACD is unknown. To examine JAML’s role in the local inflammatory response to contact allergens, we used various mouse models of ACD in JAML knockout (KO) and wild-type (WT) mice. The ear thickness was reduced by 50% (p<0.0001) in JAML KO mice compared to WT mice concomitant with a significant decrease in the production of CXCL2 and CXCL5 following the challenge with experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB). We found that 68±7% of CD8+ TRM cells express JAML and that its loss leads to decreased numbers of IFNγ-producing CD8+ TRMcells by approximately 2-fold (p=0.0258). Finally, by analyzing three publicly available gene expression datasets, we show that patients with ACD exhibit increased JAML expression in the skin. Together, our study is the first to present an essential role of JAML in the inflammatory responses to contact allergens and enlighten a new possible target for the treatment of ACD.