Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago, 310 Great King Street, Dunedin, 9054, New Zealand.
Arch Dermatol Res. 2018 Jul;310(5):431-441. doi: 10.1007/s00403-018-1829-5. Epub 2018 Apr 9.
Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by the release of cytokines by activated T-cells. Recently, the role of novel cytokines including IL33 and IL35 has been described in various chronic inflammatory diseases. IL33, a member of the IL-1 superfamily of cytokines, functions as an 'alarmin' released after cell necrosis to alert the immune system to tissue damage or stress. IL35, a member of IL12 cytokine family, is produced by regulatory T-cells and suppresses the immune response. The expression of IL33 and IL35 is yet to be investigated in OLP. The aim of this study was to determine the presence and topographical distribution of IL33 and IL35 in OLP using immunohistochemistry and quantitative real-time reverse transcriptase polymerase chain reaction (qPCR). For IHC, formalin-fixed paraffin-embedded archival specimens of OLP (n = 10) and a non-specific inflammatory (NSI) control group (n = 9) were used. A double-labelling immunofluorescence technique was used to determine the expression of IL33 and IL35 on CD3 T-cells. In addition, 12 fresh tissue samples (OLP n = 6 and NSI controls n = 6) were used to determine the gene expression of IL33 and EBI3 (one chain of the dimeric IL35). Quantitative and qualitative analysis was performed with statistical significance set at p < 0.05. IHC showed positive immunostaining with IL33 and IL35 in both OLP and NSI. Comparison of the numbers of IL33 and IL35 cells in OLP and NSI did not show any significant difference. In OLP, there were significantly more IL33 cells in the deeper connective tissue region than at the epithelial-connective tissue interface. Interestingly, all IL35 cells observed in both OLP and NSI tissues showed ovoid/plasmacytoid morphology. Double-labelling immunofluorescence showed that IL33 and IL35 expression was not localized within CD3 T-cells. The gene expression experiments showed significantly higher expression of EBI3 (fold regulation 14.02) in OLP when compared to the inflammatory controls. IL33 gene expression was not different between the groups. However, within the OLP tissues, there was a significantly higher expression of IL33 than EBI3. Our data demonstrate the expression of IL33 and IL35 in OLP lesions. Further studies are needed to understand the functional role of these cytokines in OLP pathogenesis.
口腔扁平苔藓（OLP）是一种复杂的免疫性疾病，部分由激活的 T 细胞释放细胞因子介导。最近，新型细胞因子（包括 IL33 和 IL35）在各种慢性炎症性疾病中的作用已被描述。IL33 是细胞因子白细胞介素-1 超家族的成员，作为细胞坏死释放的“警报素”，可提醒免疫系统组织损伤或应激。IL35 是 IL12 细胞因子家族的成员，由调节性 T 细胞产生，并抑制免疫反应。OLP 中尚未研究 IL33 和 IL35 的表达。本研究旨在通过免疫组织化学和实时定量逆转录聚合酶链反应（qPCR）检测 OLP 中 IL33 和 IL35 的存在和分布。对于免疫组化，使用福尔马林固定石蜡包埋的 OLP 存档标本（n=10）和非特异性炎症（NSI）对照组（n=9）。使用双标记免疫荧光技术检测 CD3 T 细胞上 IL33 和 IL35 的表达。此外，使用 12 个新鲜组织样本（OLP n=6 和 NSI 对照组 n=6）确定 IL33 和 EBI3（IL35 二聚体的一条链）的基因表达。通过定量和定性分析，统计学意义设为 p<0.05。免疫组化显示 OLP 和 NSI 中均有 IL33 和 IL35 的阳性免疫染色。OLP 和 NSI 中 IL33 和 IL35 细胞数量的比较无显著差异。在 OLP 中，深层结缔组织区域的 IL33 细胞明显多于上皮-结缔组织界面。有趣的是，在 OLP 和 NSI 组织中观察到的所有 IL35 细胞均呈卵圆形/浆细胞样形态。双标记免疫荧光显示 IL33 和 IL35 的表达不在 CD3 T 细胞内定位。基因表达实验显示，与炎症对照组相比，OLP 中 EBI3 的表达明显更高（倍数调节 14.02）。两组之间的 IL33 基因表达无差异。然而，在 OLP 组织中，IL33 的表达明显高于 EBI3。我们的数据表明，IL33 和 IL35 在 OLP 病变中表达。需要进一步研究以了解这些细胞因子在 OLP 发病机制中的功能作用。
