Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases.
Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases.
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自身免疫性甲状腺疾病患者中 Toll 样受体活性和 TLR 配体增加
DOI：
10.3389/fimmu.2016.00578
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发表时间：
2016
影响因子：
7.3
通讯作者：
Teng W
中科院分区：
文献类型：
--
作者：
Peng S;Li C;Wang X;Liu X;Han C;Jin T;Liu S;Zhang X;Zhang H;He X;Xie X;Yu X;Wang C;Shan L;Fan C;Shan Z;Teng W
目的自身免疫性甲状腺疾病（AITD）是一种由环境和遗传因素共同作用引起的器官特异性疾病。Toll样受体（TLR）是在单核细胞上大量表达的模式识别受体。关于AITD中TLR表达的数据很少。本研究的目的是检查从未经治疗的AITD患者和健康对照中提取的外周血单核细胞（PBMC）中TLR的表达、活化、配体和下游信号转导衔接子。方法分离30例健康对照者、36例桥本甲状腺炎患者和30例初发Graves病患者的PBMC。TLR mRNA，蛋白质表达，TLR配体和TLR接头分子采用实时PCR，Western印迹，流式细胞术和酶联免疫吸附试验（ELISA）进行测量。用TLR激动剂模拟PBMC。使用MTT测定评价TLR激动剂对人PBMC活力的影响。通过ELISA测定细胞培养物上清液中的促炎细胞因子白细胞介素（IL）-6、肿瘤坏死因子α（TNF-α）和IL-10。结果AITD患者TLR 2、TLR 3、TLR 9、TLR 10 mRNA表达均较正常对照组明显升高。在基线和TLR激动剂刺激下，患者单核细胞上的TLR 2、TLR 3、TLR 9、高迁移率族蛋白1（HMGB 1）和TGF 1 α表达高于对照组。TLR激动剂可显著增加AITD患者PBMC中TNF-α和IL-6的释放，而IL-10则显著降低。AITD患者TLR下游靶点、髓样分化因子88（MyD 88）和髓样toll/IL-1受体结构域（含衔接子诱导干扰素-β）显著升高。与对照组相比，AITD患者TLR 2配体、HMGB 1和热休克蛋白60水平显著升高，并与TgAb和TPOAb呈正相关，而SHP浓度在AITD患者中显著降低。结论本研究首次发现AITD患者PBMC中TLR 2、TLR 3、TLR 9表达和活化增强，TLRs可能参与了AITD的发病机制。
Objective Autoimmune thyroid disease (AITD) is an organ-specific disorder due to the interplay between environmental and genetic factors. Toll-like receptors (TLRs) are pattern recognition receptors expressed abundantly on monocytes. There is a paucity of data on TLR expression in AITD. The aim of this study was to examine TLR expression, activation, ligands, and downstream signaling adaptors in peripheral blood mononuclear cells (PBMCs) extracted from untreated AITD patients and healthy controls. Method We isolated PBMC of 30 healthy controls, 36 patients with untreated Hashimoto’s thyroiditis, and 30 patients with newly onset Graves’ disease. TLR mRNA, protein expression, TLR ligands, and TLR adaptor molecules were measured using real-time PCR, Western blot, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). PBMC was simulated with TLR agonists. The effects of TLR agonists on the viability of human PBMC were evaluated using the MTT assay. The supernatants of cell cultures were measured for the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-10 by ELISA. Results TLR2, TLR3, TLR9, and TLR10 mRNA were significantly increased in AITD patients compared with controls. TLR2, TLR3, TLR9, high mobility group box 1 (HMGB1), and RAGE expression on monocytes was higher in patients than control at baseline and TLR agonists’ stimulation. The release of TNF-α and IL-6 was significantly increased in PBMCs from AITD patients with TLR agonists, while IL-10 was significantly decreased. Downstream targets of TLR, myeloid differentiation factor 88 (MyD88), and myeloid toll/IL-1 receptor-domain containing adaptor-inducing interferon-β were significantly elevated in AITD patients. Levels of TLR2 ligands, HMGB1, and heat shock protein 60 were significantly elevated in AITD patients compared with those in controls and positively correlated with TgAb and TPOAb, while sRAGE concentration was significantly decreased in AITD patients. Conclusion This work is the first to show that TLR2, TLR3, and TLR9 expression and activation are elevated in the PBMCs of patients with AITD and TLRs may participate in the pathogenesis of AITD.
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影响因子：
3.8
作者：
Gammazza, Antonella Marino;Rizzo, Manfredi;Cappello, Francesco
通讯作者：
Cappello, Francesco
影响因子：
3.5
作者：
Kotani, T;Aratake, Y;Ohtaki, S
通讯作者：
Ohtaki, S
TLR7 MyD88依赖性信号通路参与成人发病的发病机理。
影响因子：
4.9
作者：
Chen DY;Lin CC;Chen YM;Lan JL;Hung WT;Chen HH;Lai KL;Hsieh CW
通讯作者：
Hsieh CW
影响因子：
--
作者：
Liao WL;Chen RH;Lin HJ;Liu YH;Chen WC;Tsai Y;Wan L;Tsai FJ
通讯作者：
Tsai FJ
影响因子：
3.1
作者：
Pace, Andrea;Barone, Giampaolo;Macario, Alberto J. L.
通讯作者：
Macario, Alberto J. L.