Mucosal-Associated Invariant T Cells in Health and Disease

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individuals, MAIT cells maintain mucosal barrier integrity, participate in tissue repair after injury, and prevent excessive inflammation. In microbial infections, MAIT cells eliminate infected cells and modulate immune responses or become pathogenic when overactivated by superantigens. In the context of immune-related diseases, MAIT cells migrate to inflamed tissues and become pathogenic by secreting tissue-damaging cytokines or protective by modulating immune responses. Moreover, MAIT cells have been demonstrated to have therapeutic applications in controlling diseases through their use as cellular adjuvants, their increased activation by engineered bacteria, and their modification with chimeric antigen receptors. This review synthesizes the functional plasticity of MAIT cells in health and disease, highlighting the therapeutic efficacy and limitations of engineered MAIT cells for precise intervention.