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.
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.
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.
摘要：
目的：口腔扁平苔藓（OLP）是一种慢性炎症性疾病，其特征是密集的T细胞浸润和基底角质形成细胞的变性。在我们先前的研究中已经分析了OLP中粘膜相关不变T（MAIT）细胞的潜在功能。已经证明在促炎条件下的角质形成细胞激活T细胞。本研究旨在探讨角质形成细胞如何刺激OLP中的MAIT细胞。并探讨活化的MAIT细胞对角质形成细胞的作用。
结果：通过流式细胞术在OLP病变中检测到MAIT细胞增加和更高的活化标志物CD69。通过免疫组织化学确定OLP病变上皮层中MAIT细胞活化所需的MHCI类分子（MR1）的增强表达。用5-A-RU前药和脂多糖处理的角质形成细胞，分别,表现出更高的MR1表达和IL-18分泌。在由角质形成细胞和外周血单核细胞组成的直接共培养系统中，5-A-RU前药预处理的角质形成细胞和脂多糖预处理的角质形成细胞都激活MAIT细胞分泌颗粒酶B，促进角质形成细胞凋亡。
结论：角质形成细胞能够通过MR1和OLP中的细胞因子激活MAIT细胞，激活的MAIT细胞产生的颗粒酶B增强了角质形成细胞的凋亡，参与OLP的发病机制。
结果：通过流式细胞术在OLP病变中检测到MAIT细胞增加和更高的活化标志物CD69。通过免疫组织化学确定OLP病变上皮层中MAIT细胞活化所需的MHCI类分子（MR1）的增强表达。用5-A-RU前药和脂多糖处理的角质形成细胞，分别,表现出更高的MR1表达和IL-18分泌。在由角质形成细胞和外周血单核细胞组成的直接共培养系统中，5-A-RU前药预处理的角质形成细胞和脂多糖预处理的角质形成细胞都激活MAIT细胞分泌颗粒酶B，促进角质形成细胞凋亡。
结论：角质形成细胞能够通过MR1和OLP中的细胞因子激活MAIT细胞，激活的MAIT细胞产生的颗粒酶B增强了角质形成细胞的凋亡，参与OLP的发病机制。
