Zake Tatjana, Skuja Sandra, Kalere Ieva, Konrade Ilze, Groma Valerija
Institute of Anatomy and Anthropology Department of Internal Medicine, Riga Stradins University, Riga, Latvia.
Medicine (Baltimore). 2018 Jun;97(25):e11211. doi: 10.1097/MD.0000000000011211.
Th17 cells together with their hallmark cytokine interleukin (IL)-17 were identified as crucial contributing factors in the pathogenesis of thyroid autoimmunity. The cytokine-regulated tight junction (Tj) disruption is thought to be essential in the initiation and/or development of several diseases. Still, the role of IL-17 maintaining Tj integrity in autoimmune thyroid diseases (AITDs) has not yet been evaluated. We aimed to investigate integrity of the thyroid follicle by studying immunoexpression of cellular Tj - zonula occludens (ZO)-1 and claudin-1 proteins coupled to IL-17A and CD68 detection in AITD patients compared with controls.Thirty-five adult patients undergoing thyroidectomy and presenting 18 cases of Hashimoto thyroiditis (HT), 7 of Graves' disease (GD) as well as 10 subjects of colloid goiter without autoimmune component served as controls were enrolled in this study. An immunohistochemical analysis including IL-17A, ZO-1, claudin-1, and CD68 detection was performed in each case. The correlation of IL-17A with Tj and CD68 in patients with AITD was also analyzed.Apart from inflammatory cells, we evidenced a stronger expression level of IL17A in the thyroid follicular cells in HT patients when compared with GD or colloid goiter. A significant reduction of ZO-1 immunoreactivity was observed in the thyrocytes in HT patients, whereas no significant differences were found in claudin-1 expression in HT and GD compared with colloid goiter patients. A significantly higher number of thyroid follicles with CD68-positive cells was found in HT patients than that in patients with GD or colloid goiter. In HT patients, the expression of IL-17A in the follicular cells was positively correlated with CD68 immunopositivity, whereas no association with claudin-1 or ZO-1 expression was found. GD patients did not reveal any significant correlation of IL-17A with Tj and CD68.Strong overexpression of IL-17A observed in the thyroid epithelial cells is associated with the presence of intrafollicular CD68-positive cells in HT patients. We evidenced the changes in molecules of thyrocyte junctional complexes highlighting impairment of the thyroid follicle integrity in HT, but no association with IL-17A was found.
Th17细胞及其标志性细胞因子白细胞介素(IL)-17被确定为甲状腺自身免疫发病机制中的关键促成因素。细胞因子调节的紧密连接(Tj)破坏被认为在几种疾病的发生和/或发展中至关重要。然而,IL-17在自身免疫性甲状腺疾病(AITD)中维持Tj完整性的作用尚未得到评估。我们旨在通过研究细胞Tj - 闭合蛋白(ZO)-1和claudin-1蛋白的免疫表达,并结合IL-17A和CD68检测,来调查AITD患者与对照组相比甲状腺滤泡的完整性。
本研究纳入了35例接受甲状腺切除术的成年患者,其中18例为桥本甲状腺炎(HT),7例为格雷夫斯病(GD),另外10例无自身免疫成分的胶体甲状腺肿患者作为对照。对每个病例进行了包括IL-17A、ZO-1、claudin-1和CD68检测的免疫组织化学分析。还分析了AITD患者中IL-17A与Tj和CD68的相关性。
除炎症细胞外,我们发现与GD或胶体甲状腺肿相比,HT患者甲状腺滤泡细胞中IL17A的表达水平更高。在HT患者的甲状腺细胞中观察到ZO-1免疫反应性显著降低,而与胶体甲状腺肿患者相比,HT和GD患者中claudin-1表达未发现显著差异。HT患者中CD68阳性细胞的甲状腺滤泡数量显著高于GD或胶体甲状腺肿患者。在HT患者中,滤泡细胞中IL-17A的表达与CD68免疫阳性呈正相关,而与claudin-1或ZO-1表达无关联。GD患者中IL-17A与Tj和CD-68未显示任何显著相关性。
在HT患者中,甲状腺上皮细胞中观察到的IL-17A强烈过表达与滤泡内CD68阳性细胞的存在有关。我们证明了甲状腺细胞连接复合体分子的变化,突出了HT中甲状腺滤泡完整性的损害,但未发现与IL-17A有关联。