Dendritic cells maturation in the oral lichen planus as a target for treatment

口腔扁平苔藓是一种病因不明的口腔扁平苔藓，其组织学特征为黏膜上皮基底层下有带状T细胞浸润。Killer T和NK细胞渗入基底层，提示基底层细胞变性。在口腔扁平苔藓病变中发现的树突状细胞(DC)也可能是控制病变的重要细胞因子。然而，这些细胞的浸润机制尚不清楚。DC迁移病变后，局部合成花生四烯酸前列腺素E_2(PGE_2)诱导DC成熟。因此，我们制定了一项利用组蛋白脱乙酰酶抑制剂抑制花生四烯酸合成来调节DC功能的计划。我们首先检测了口腔扁平苔藓病变的环氧合酶2(COX2)和磷脂酶A2的表达，这两种酶与口腔黏膜上特有的白色外观有关。COX2的过度表达与上皮厚度和棘细胞数量呈正相关。明确发现亚群特异的磷脂酶A2、磷脂酶A_2-V和磷脂酶…上皮细胞中A2-X较多，PLA2-IIa较少。体外实验证明，剂量依赖性地下调NaBu通过sPLA2和COX2的表达来下调PGE2的产生。但PGE2在CD8阳性细胞和NK细胞损伤后的上皮细胞修复中起一定作用。COX2在皮损中的过度表达可能与口腔扁平苔藓的恶变有关。因此，进一步的实验需要阐明控制OLP的关键机制。我们还建立了一种模拟口腔扁平苔藓的口腔粘膜迟发性增生的小鼠实验模型。在本研究中，我们评估了参与口腔扁平苔藓病变发展的细胞和细胞因子，为开发有用的治疗系统奠定了基础。我们的结果清楚地表明，NK细胞在病变的早期发展中起着关键作用。用asialo GM1抗体处理NK细胞的缺失，表明小鼠由于淋巴细胞募集障碍而明显减轻了迟发型超敏反应的严重程度。IL-2和INF-？是参与病变细胞浸润的主要细胞因子。较少

Oral lichen planus is characterized histological by band-like T cells infiltration just under the basal cell layer of mucosal epithelium with unknown etiology. The Killer T and NK cell infiltration into the basal cell layer, indicated degeneration of basal cells. Dendritic cell (DC) found in the lesion of OLP may also important cell elements for controlling the lesion. However, the mechanism of these cells infiltration was not clarified yet. After DC migrated the lesion, DC revealed maturation by local synthesized arachidonate, PGE2. Thus, we made a plan to regulate DC function with suppression of arachidonate synthesis using histone deacethyrase inhibitor.We first examined cyclooxigenase 2 (COX2) and Phospholipase A2 expression of the OLP lesion, which relate to characteristic white color appearance on oral mucosa. COX2 over expression paralleled to thickness of epithelium and amounts of prickle cells in the epithelium. Clear finding obtained that subgroup specific PLA2, PLA2-V and PL … More A2-X but not for PLA2-IIa, were identified in the epithelium. In vitro experiment demonstrates dose dependent down regulate the PGE2 production by NaBu through the sPLA2 and COX2 expression. However, PGE2 play a role for the epithelial cell repair following epithelial cells received damage by CD8 positive cell and NK cells. More over the COX2 overexpression in the lesions may be related to malignant transformation of OLP. Thus, further experiments required elucidating critical mechanism for controlling the OLP. We also have developed a mouse experimental model of oral mucosal delayed type hyperplasia as a mimic of OLP. In this study, we have valuated the cells and cytokine involve development the OLP lesion for the development of useful treatment system. Our result clearly indicted that NK cell play key role for the early development of the lesion. NK cells deletion with asialo GM1 antibody administration indicated that mouse was clearly showed decrease the severity of DTH due to the disturbance of lymphocytes recruitment. IL-2 and INF-? are major cytokines involved in cell infiltration of the lesion. Less