MR1 ‐Mediated Activation of Mucosal‐Associated Invariant T Cells by Oral Lichen Planus‐Associated Fibroblasts

ABSTRACT Background Oral lichen planus (OLP) is a chronic immune‐mediated inflammatory disease with malignant potential, and its local inflammatory microenvironment is closely related to mucosal‐associated invariant T cells (MAIT). Our prior work established OLP‐associated fibroblasts (OLP/AFs) in creating the inflammatory milieu, but their interaction with MAIT cells remains unexplored. This study aims to investigate how OLP/AFs interact with MAIT cells. Materials and Methods Oral mucosal samples from OLP patients and healthy controls were selected for flow cytometry to detect MAIT cells. MR1 expression on fibroblasts was quantified via RT‐qPCR, Western blot, immunohistochemistry, and immunofluorescence. For functional assays, OLP/AFs were stimulated with formaldehyde‐fixed Escherichia coli ( E. coli ) to induce MR1 surface expression, then co‐cultured with PBMCs±anti‐MR1 blocking antibody and evaluated the activation status of MAIT. Results MR1 expression and MR1 + fibroblast density were significantly elevated in OLP lesions compared to healthy controls. OLP/AFs demonstrated higher baseline MR1 expression than normal fibroblasts, which was further enhanced following E. coli stimulation. Co‐culture of E. coli ‐stimulated OLP/AFs with peripheral blood mononuclear cells induced marked activation of MAIT cells. This was evidenced by significantly increased frequencies of CD69 + MAIT cells and elevated secretion of pro‐inflammatory cytokines and cytotoxic molecules. Conclusion OLP/AFs activate MAIT cells via an MR1‐dependent mechanism.