Immunosuppressive role of mucosal-associated invariant T (MAIT) cells in inflammatory skin disease 2798

Abstract Description MAIT cells are functionally diverse innate-like lymphocytes that recognize microbial-derived antigens. While MAIT cells can exhibit both tissue repair and cytotoxic properties, their role in chronic inflammatory skin disease is unknown. Using MAIT cell specific tetramer, we found that MAIT cells are reduced in skin of mice that develop chronic inflammatory skin disease, mimicking human cutaneous lupus erythematosus (CLE). Like human lupus skin, MAIT cell levels are ∼10-fold lower in pre-lesional skin of young MRL-lpr lupus-prone mice, compared to control MRL-MpJ or C57Bl/6 skin. MAIT cells in CLE-like skin have an activated/exhausted phenotype. Topical dosing of MAIT cell antigen, 5-OP-RU, expands MAIT cells in MRL-lpr skin, decreases expression of inflammatory (Il6, Tnf) and cytotoxic (Gzmb, Ifng) genes, and stimulates local Treg expansion. Treg do not expand with topical 5-OP-RU in MAIT-deficient, confirming Treg expansion is MAIT cell dependent. Of therapeutic relevance, short-term expansion of skin MAIT cells results in complete and lasting resolution of severe skin lesions in MRL-lpr mice, while vehicle-treated mice never fully heal. These data suggest that the absence of MAIT cells may contribute to pathogenesis of chronic skin inflammation and that MAIT cell-driven immunosuppression in the skin may be mediated via Treg expansion. Overall, these findings have implications for skin disease in systemic LE (SLE), one of the leading causes of death in young females. Funding Sources T32 AI007363 NIAMS R01AR080641 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)