083 CXCR4-expressing Skin-Resident NKT Cells Develop Allergic Inflammation in Atopic Dermatitis

Adaptive allergic inflammation plays key roles in atopic dermatitis (AD). However, it is challenging for non-allergic AD or recalcitrant severe AD patients, which demand new immunological therapies such as targeting innate immunity to control these symptoms. NKT cells share cell-surface proteins with conventional T cells and NK cells that serve as unconventional T cells bridging between innate and adaptive immunity. NKT cells are known for a new player to develop AD, which are collaborated with several chemokines that increase in atopic dermatitis. In this study, we identified that CXCR4 and its cognate ligand CXCL12 were significantly up-regulated in human AD skin by proteomic and transcriptomic analyses, which were consistently elevated in our AD mouse model. Adoptive transfer of allergen-specific NKT cells conferred antigen-specific cutaneous inflammation in our model, and predominant skin NKT cells were CXCR4+ and CD69+, indicating a type of resident memory T cells. By intravital imaging, we also found that CXCR4+ NKT preferentially traffic to CXCL12-rich area formed an enriched skin-resident NKT cluster. Taken together, our results suggest that CXCR4+ skin-resident NKT cells may play an essential role in the pathogenesis of atopic dermatitis.