Increased Circulating Pro-Inflammatory Cytokines and Th17 Lymphocytes in Hashimoto's Thyroiditis

Increased Circulating Pro-Inflammatory Cytokines and Th17 Lymphocytes in Hashimoto's Thyroiditis
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DOI:
10.1210/jc.2009-1719
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发表时间:
2010-02-01
影响因子:
5.8
通讯作者:
Marazuela, Monica
Marazuela, Monica
中科院分区:
医学2区
文献类型:
--
作者:
Figueroa-Vega, Nicte;Alfonso-Perez, Manuel;Marazuela, Monica

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内容:Th17淋巴细胞在不同的慢性炎症和自身免疫性疾病中发挥重要作用。目的:本研究的目的是探讨自身免疫性甲状腺疾病(AITD)患者Th17细胞的状态。设计:我们评估了IL-17和IL-22以及不同细胞因子的血清水平和体外合成IL-6、IL-15和IL-23参与了26例AITD患者、8例Graves病患者、18例桥本甲状腺炎(HT)患者以及10名健康对照者外周血和甲状腺中Th17细胞的分化。我们发现AITD患者外周血中合成IL-17和IL-22的T细胞水平增加,主要是在HT患者中。此外,与Graves病或对照组相比,HT患者甲状腺中IL-17和IL-22的表达更强,IL-23 R(+)细胞数量增加。此外,HT患者血清中检测到IL-6和IL-15浓度升高,而这些患者血清中IL-23水平往往较高。最后,在AITD患者中观察到IL-23/IL-6诱导的T淋巴细胞向Th17细胞的体外分化增强。结论:AITD患者Th17淋巴细胞分化增强,Th17细胞因子合成增加,以HT为主。这些现象可能在甲状腺自身免疫的发病机制中起重要作用。(临床内分泌代谢杂志95:953 - 962,2010)
Context: Th17 lymphocytes play an important role in different chronic inflammatory and autoimmune conditions.Aim: The aim of the study was to explore the status of Th17 cells in patients with autoimmune thyroid diseases (AITD).Design: We assessed the serum levels and in vitro synthesis of IL-17 and IL-22 and of different cytokines (IL-6, IL-15, and IL-23) involved in the differentiation of Th17 cells in the peripheral blood and thyroid glands of 26 patients with AITD, eight with Graves' disease, and 18 with Hashimoto's thyroiditis (HT) as well as 10 healthy controls.Results: We found enhanced levels of T cells synthesizing IL-17 and IL-22 in the peripheral blood from AITD patients, mainly in those with HT. In addition, a stronger expression of IL-17 and IL-22 and an enhanced number of IL-23R(+) cells was detected in thyroid glands from HT patients compared with Graves' disease or controls. Furthermore, increased concentrations of IL-6 and IL-15 were detected in sera from HT patients, whereas serum levels of IL- 23 tended to be higher in these patients. Finally, an enhanced in vitro differentiation of T lymphocytes into Th17 cells induced by IL-23/IL-6 was observed in AITD patients. Accordingly, a strong induction of RORC2 gene was detected in lymphocytes from HT patients when stimulated with IL-23.Conclusion: Our results indicate that there is an increased differentiation of Th17 lymphocytes and an enhanced synthesis of Th17 cytokines in AITD, mainly in HT. These phenomena may have an important role in the pathogenesis of thyroid autoimmunity. (J Clin Endocrinol Metab 95: 953-962, 2010)