OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T-cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes.
RESULTS: Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I-like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5-A-RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL-18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5-A-RU prodrug-pretreated keratinocytes and lipopolysaccharide-pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis.
CONCLUSIONS: Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.

Mucosal-associated invariant T (MAIT) cells have a semi-invariant T-cell receptor that allows recognition of antigen in the context of the MHC class I-related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1-restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon-gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL-17. Given that MAIT cells are present in human barrier tissues colonized by a microbiome, MAIT cells must somehow be able to distinguish colonization from infection to ensure effector functions are only elicited when necessary. Importantly, MAIT cells have additional functional properties, including the potential to contribute to restoring tissue homeostasis by expression of CTLA-4 and secretion of the cytokine IL-22. A recent study provided compelling data indicating that the range of human MAIT cell functional properties is explained by plasticity rather than distinct lineages. This further underscores the necessity to better understand how different signals regulate MAIT cell function. In this review, we highlight what is known in regards to activating and inhibitory signals for MAIT cells with a specific focus on signals relevant to healthy and inflamed tissues. We consider the quantity, quality, and the temporal order of these signals on MAIT cell function and discuss the current limitations of computational tools to extrapolate which signals are received by MAIT cells in human tissues. Using lessons learned from conventional CD8 T cells, we also discuss how TCR signals may integrate with cytokine signals in MAIT cells to elicit distinct functional states.