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

Oral Dis. 2025 Jan;31(1):148-159. doi: 10.1111/odi.15057. Epub 2024 Jun 27.

Abstract

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.

Methods and 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.

Keywords: IL‐18; MR1; granzyme B; keratinocyte; mucosal‐associated invariant T cell; oral lichen planus.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Apoptosis
  • CD69 Antigens
  • Coculture Techniques
  • Cytokines* / metabolism
  • Female
  • Granzymes* / biosynthesis
  • Granzymes* / metabolism
  • Histocompatibility Antigens Class I* / metabolism
  • Humans
  • Interleukin-18 / metabolism
  • Keratinocytes* / immunology
  • Keratinocytes* / metabolism
  • Keratinocytes* / physiology
  • Lectins, C-Type / metabolism
  • Lichen Planus, Oral* / immunology
  • Lichen Planus, Oral* / metabolism
  • Lichen Planus, Oral* / pathology
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens* / metabolism
  • Mucosal-Associated Invariant T Cells* / immunology
  • Mucosal-Associated Invariant T Cells* / metabolism

Substances

  • Granzymes
  • Histocompatibility Antigens Class I
  • Minor Histocompatibility Antigens
  • Cytokines
  • Interleukin-18
  • Antigens, Differentiation, T-Lymphocyte
  • Lectins, C-Type
  • Lipopolysaccharides
  • Antigens, CD
  • CD69 Antigens
  • MR1 protein, human