Kemp E Helen, Metcalfe Russell A, Smith Karen A, Woodroofe M Nicola, Watson Philip F, Weetman Anthony P
Division of Clinical Sciences (North), University of Sheffield, Northern General Hospital, UK.
Clin Endocrinol (Oxf). 2003 Aug;59(2):207-13. doi: 10.1046/j.1365-2265.2003.01824.x.
Autoimmune thyroid disease (Hashimoto's thyroiditis and Graves' disease) is characterized by lymphocytic infiltration of the thyroid gland. Chemokines are cytokines with chemoattractant properties for a range of immune effector cells and might therefore play a significant role in the initiation and maintenance of the autoimmune process. The aim of this study was to analyse chemokine gene expression in autoimmune thyroid tissue and in cultured thyroid follicular cells (TFC).
Immunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification were used to analyse the expression of monocyte chemoattractant protein (MCP)-1, RANTES (regulated upon activation, normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interferon (IFN)-gamma-inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig) in thyroid tissue from patients with Hashimoto's thyroiditis (n = 4), Graves' disease (n = 6) and nonautoimmune multinodular goitre (n = 4). Chemokine gene expression was also examined in cultured TFC by RT-PCR.
Expression of MCP-1, RANTES, MIP-1 alpha, MIP-1 beta, IP-10 and Mig was demonstrated in all Hashimoto's and most Graves' thyroid specimens but very little expression was detected in the nonautoimmune goitre samples. In thyroid tissue from Graves' disease patients, positive staining for chemokines was largely restricted to the lymphocytic cell infiltrate. Within thyroid tissue from Hashimoto's patients, there was evidence for the expression of all chemokines by thyroid follicular cells, suggesting a role for local chemokine synthesis by the glandular epithelial cells in the recruitment of inflammatory cells into the gland in autoimmunity. The present work also showed that expression all the chemokine genes analysed could be induced in cultured thyroid cells by IFN-gamma and interleukin (IL)-1 alpha. Expression of all the chemokines examined was not stimulated by TSH.
We postulate that TFC may play a role in the pathogenesis of autoimmune thyroid disease as they are able to express the chemokines MIP-1 alpha, MIP-1 beta, MCP-1, RANTES, IP-10 and Mig that would promote the infiltration of immune cells into the thyroid gland.
自身免疫性甲状腺疾病（桥本甲状腺炎和格雷夫斯病）的特征是甲状腺出现淋巴细胞浸润。趋化因子是一类对多种免疫效应细胞具有趋化作用的细胞因子，因此可能在自身免疫过程的启动和维持中发挥重要作用。本研究的目的是分析自身免疫性甲状腺组织和培养的甲状腺滤泡细胞（TFC）中趋化因子基因的表达情况。
采用免疫细胞化学和逆转录聚合酶链反应（RT-PCR）扩增技术，分析单核细胞趋化蛋白（MCP）-1、调节激活正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、干扰素（IFN）-γ诱导蛋白（IP）-10和IFN-γ诱导的单核因子（Mig）在桥本甲状腺炎患者（n = 4）、格雷夫斯病患者（n = 6）和非自身免疫性多结节性甲状腺肿患者（n = 4）的甲状腺组织中的表达。还通过RT-PCR检测培养的TFC中趋化因子基因的表达。
在所有桥本甲状腺炎和大多数格雷夫斯病甲状腺标本中均检测到MCP-1、RANTES、MIP-1α、MIP-1β、IP-10和Mig的表达，但在非自身免疫性甲状腺肿样本中检测到的表达极少。在格雷夫斯病患者的甲状腺组织中，趋化因子的阳性染色主要局限于淋巴细胞浸润部位。在桥本甲状腺炎患者的甲状腺组织中，有证据表明甲状腺滤泡细胞表达所有趋化因子，提示腺上皮细胞局部合成趋化因子在自身免疫中炎症细胞向腺体内募集过程中发挥作用。本研究还表明，IFN-γ和白细胞介素（IL）-1α可诱导培养的甲状腺细胞中所有分析的趋化因子基因表达。促甲状腺激素（TSH）未刺激所检测的所有趋化因子的表达。
我们推测TFC可能在自身免疫性甲状腺疾病的发病机制中发挥作用，因为它们能够表达趋化因子MIP-1α、MIP-1β、MCP-1、RANTES、IP-10和Mig，这些趋化因子会促进免疫细胞浸润到甲状腺中。
