Lu Yi, Wu Yu, Huang Yazhuo, Fang Sijie, Li Yinwei, Sun Jing, Zhou Huifang
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai Ninth People's Hospital, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Feb 10;11:621321. doi: 10.3389/fendo.2020.621321. eCollection 2020.
Previous studies showed that patients with Graves' orbitopathy (GO) had concomitant mucosal abnormality within the paranasal sinuses. It remains unknown whether the immunological reactions in sinus mucosa affect the orbit inflammation in GO.
Patients with GO underwent sinus computed tomography (CT) scans for sinus mucosal disease by two independent reviewers using the Lund-MacKay systems. Ethmoid mucosal samples were collected during orbital decompression surgeries for patients with GO and correction surgeries for patients with old orbital fractures as controls. Histological analysis and immunofluorescence were performed in all sinus mucosa tissues. Flow cytometry analysis was used to examine the immunological features of sinus mucosa in both GO and control groups.
Immunohistochemistry showed that the paranasal sinus mucosa of patients with GO grew swelling, with goblet cell and small vessel proliferation, endothelial cell swelling, and inflammatory cell infiltration. The number of T helper (Th)1, Th17, and gamma-delta T cells in nasal sinus mucosa of patients with GO increased significantly compared with those from controls. Further, the proportion of Th1 cells was significantly correlated with clinical activity score. In addition, there was a decreased number of regulatory T cells in patients with GO. The number of Th2 cells showed no significant difference between the two groups. Finally, the proportion of interleukin-22-producing cell subsets in gamma-delta T cells of patients with GO was significantly increased compared with those from controls.
Our observations illustrated a potential pathogenic role of mucosal-infiltrating T cells, which may have the possibility to aggravate inflammatory responses in GO.
既往研究表明,格雷夫斯眶病(GO)患者伴有鼻窦内黏膜异常。鼻窦黏膜中的免疫反应是否会影响GO的眼眶炎症仍不清楚。
采用伦德-麦凯系统,由两名独立的评估者对GO患者进行鼻窦计算机断层扫描(CT)以检查鼻窦黏膜疾病。在GO患者的眼眶减压手术期间以及以陈旧性眼眶骨折患者的矫正手术作为对照时,采集筛窦黏膜样本。对所有鼻窦黏膜组织进行组织学分析和免疫荧光检查。采用流式细胞术分析GO组和对照组鼻窦黏膜的免疫特征。
免疫组织化学显示,GO患者的鼻窦黏膜肿胀,杯状细胞和小血管增生,内皮细胞肿胀,并有炎性细胞浸润。与对照组相比,GO患者鼻窦黏膜中辅助性T(Th)1细胞、Th17细胞和γδT细胞的数量显著增加。此外,Th1细胞的比例与临床活动评分显著相关。此外,GO患者的调节性T细胞数量减少。两组之间Th2细胞的数量无显著差异。最后,与对照组相比,GO患者γδT细胞中产生白细胞介素-22的细胞亚群比例显著增加。
我们的观察结果表明黏膜浸润性T细胞具有潜在的致病作用,这可能会加重GO中的炎症反应。