Keratinocytes stimulate MAIT cells to produce granzyme B via MR1 and cytokines in oral lichen planus

Abstract

AbstractObjectiveOral 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.Methods and ResultsIncreased 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.ConclusionsKeratinocytes 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.