Mucosal-associated invariant T cells and the gut-kidney axis: a review

Mucosal-associated invariant T (MAIT) cells are a distinct subset of innate-like lymphocytes that bridge microbial homeostasis and tissue immunity. These evolutionarily conserved cells are activated via the recognition of microbial metabolites presented by the MR1 molecule and establish stable residency in the kidney, where they profoundly influence local immune-metabolic processes. There is growing interest in the robust regulatory capacities of MAIT cells in renal physiology and pathology. This review systematically delineates their paradoxical roles in kidney diseases. Under specific conditions, they exert protective functions by suppressing inflammation and maintaining tissue homeostasis. Conversely, in distinct microenvironments, they adopt a pro-inflammatory phenotype, exacerbating pathological progression through the release of inflammatory cytokines and cytotoxic effector functions. The gut-kidney axis serves as a critical regulatory hub, wherein dysbiosis-derived signals can significantly amplify the renal impact of MAIT cells. Focusing on clinical translation, we provide an in-depth exploration of innovative strategies targeting MAIT cells, including adoptive cell therapy, receptor-targeting agents, and microbiome reconstruction. These approaches position MAIT cells as promising therapeutic targets for a new generation of immune-mediated kidney diseases.