Oral diseases · 2026
MR1-Mediated Activation of Mucosal-Associated Invariant T Cells by Oral Lichen Planus-Associated Fibroblasts.
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Wu Xiaoli, Mi Qian, Chen Yuhe, Xu Xiaoheng, Xiong Xiaoqin, Meng Wenxia
Аннотация
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.
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.
Предметные рубрики MeSH
HumansLichen Planus, OralMucosal-Associated Invariant T CellsFibroblastsFemaleMaleHistocompatibility Antigens Class IMinor Histocompatibility AntigensMiddle AgedLymphocyte ActivationAdultAntigens, Differentiation, T-LymphocyteLectins, C-TypeMouth MucosaAntigens, CDCase-Control StudiesCD69 AntigensCoculture TechniquesAgedFlow Cytometry