Abstract
Mucosal-associated invariant T (MAIT) cells are a highly conserved population of immune cells that can be activated via the major histocompatibility complex class I-related protein pathway or cytokine pathways, playing a central role in immune surveillance. This review provides comprehensive information on their thymic developmental origin, tissue-specific distribution, and microbial regulatory networks, with a focus on analyzing the bidirectional regulatory mechanisms in diseases. In infectious diseases, MAIT cells eliminate pathogens through the rapid release of cytokines; however, sustained antigen exposure leads to functional exhaustion. In autoimmune diseases, their migration disorders and proinflammatory cytokine secretion of MAIT cells exacerbate tissue damage. In the tumor microenvironment, they play a paradoxical role, being capable of mediating antitumor effects while also being reprogrammed into a protumor phenotype. Based on their tissue targeting ability and functional plasticity, we discuss novel strategies for targeted therapy, including engineering chimeric antigen receptor-MAIT cells to enhance tumor killing, blocking exhaustion pathways to reverse functional impairment, and regulating the microbiota-metabolic axis to reprogram cell activity. This review integrates cutting-edge evidence, reveals the translational potential of MAIT cells as a cross-disease regulatory hub, and provides a theoretical framework for precision immunotherapy.