FcεRI信号通路在泪腺良性淋巴上皮病变发病中的作用机制研究

Benign lymphepithelial lesions (BLEL) of the lacrimal gland is an orbital disease which is hidden onset and easy to relapse. At present, the pathogenesis of BLEL of the lacrimal gland is unknown, which results in poor efficacy of drugs. Some studies have suggested that BLEL of the lacrimal gland belongs to IgG4 related disease, and the pathogenesis of IgG4 related diseases is currently considered to be closely related to the activation of type 2 helper T cells and regulatory T cells. In the previous study, our research group used gene chips and immunohistochemical staining techniques, showed that FcεRI signaling pathway was involved in the pathogenesis of BLEL of the lacrimal gland. Therefore, based on the previous research results combining with our experimental results, we proposed the hypothesis that "BLEL of the lacrimal gland is an immune orbital disease which is major mediated by FcεRI signaling pathway and characterized with Th1/Th2 drift and IgG4 overexpression". Our study will research on the specific mechanisms of FcεRI signaling pathway in the pathogenesis of BLEL of the lacrimal gland. The results will provide a new evidence for the study on the etiology of IgG4 related diseases including BLEL of the lacrimal gland.

泪腺良性淋巴上皮病变（benign lymphoepithelial lesion, BLEL）是一种发病隐匿且极易复发的眼眶疾病。目前，泪腺BLEL的病因不明，导致该病药物疗效欠佳。已有研究提示泪腺BLEL属于IgG4相关性疾病，而IgG4相关性疾病的发病机制目前认为与2型辅助性T细胞及调节性T细胞的活化密切相关。在先期研究中，本课题组采用基因芯片和免疫组织化学染色技术，提示FcεRI信号通路参与了泪腺BLEL的发病过程。因此，基于前人研究成果并结合预实验结果，提出“泪腺BLEL是由FcεRI信号通路主要介导的，表现为Th1/Th2漂移及特征性IgG4过表达的一种免疫性眼病"的假说。本课题将在先期研究基础上，系统研究FcεRI信号通路与泪腺BLEL发病之间的具体作用机制。研究结果以期为包括泪腺BLEL在内的IgG4相关性疾病的病因研究提供新的依据。

目的：本研究旨在分析Fc epsilon RI（FcεRI）信号通路在发病机制中的作用。方法：收集2010年7月至2013年10月在首都医科大学附属北京同仁医院经病理组织学检查证实的泪腺良性淋巴上皮病变和眼眶海绵状血管瘤患者。随机选择2018年10月至2019年8月期间确诊的4名泪腺良性淋巴上皮病变患者和3名眼眶海绵状血管瘤患者分别为实验组和对照组。RT-PCR，免疫组化染色，western blotting用于验证与FcεRI信号通路相关的基因和蛋白质。结果：转录组学分析显示，与海绵状血管瘤组比较，FcεRI信号通路在LGBLEL中上调。SYK、p38、JNK、PI3K和ERK等重要基因的mRNA表达水平病例组相比对照组显著升高(分别为P= 0.0066，P= 0.0002，P= 0.0003，P< 0.0001，P < 0.0001)。免疫组化染色结果显示SYK、p38和ERK在LGBLEL中阳性表达，而JNK和PI3K则不表达。病例组中P-SYK、P-p38、P-JNK、P-PI3K和P-ERK蛋白的含量显著高于对照组（分别为P=0.0169、P=0.0074、P=0.0046、P=0.0157、P=0.0156）。结论：FcεRI信号通路参与LGBLEL的发病机制。