Mucosal-Associated Invariant T (MAIT) Cells in Skin Immunity: Metabolic Regulation, Tissue Adaptation, and Roles in Skin Inflammation and Disease.

Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes that recognize microbial-derived vitamin B metabolites presented by the nonpolymorphic MR1 (major histocompatibility complex class I-related protein). These cells comprise about 1-10% of circulating T cells in humans and are abundant at mucosal surfaces, including the skin. MAIT cells possess a semi-invariant TCR (typically, TRAV1-2/TRAJ33 in humans) and can be activated by riboflavin metabolites such as 5-OP-RU (5-[2-oxopropylideneamino]-6-d-ribitylaminouracil) and 5-OE-RU (5-2-oxoethylideneamino]-6-d-ribitylaminouracil) as well as through cytokine-mediated pathways independent of MR1. Upon activation, MAIT cells quickly produce proinflammatory cytokines, including IFN-γ, TNF-α, and IL-17, and perform cytotoxic functions by releasing granzyme B and perforin. This review thoroughly explores the role of MAIT cells in skin immunity and skin diseases. We detail their involvement in inflammatory skin conditions such as psoriasis, atopic dermatitis, and hidradenitis suppurativa, where alterations in MAIT cell numbers and functions have been observed. The review also addresses MAIT cells' roles in wound healing, tissue repair, and antimicrobial defense within the skin. Furthermore, we evaluate the potential of targeting MAIT cells for therapy, including how current treatments affect them and the development of new immunometabolic strategies. Gaining a better understanding of MAIT cell biology in skin contexts could provide new insights into the development of skin diseases and lead to innovative dermatological treatments.