Experimental autoimmune thyroiditis and/or sialadenitis induced by sodium iodide symporter

碘化钠同向转运蛋白诱导的实验性自身免疫性甲状腺炎和/或唾液腺炎

• 批准号: 13672423
• 负责人: HIDAKA Yoh
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672423/
• 关键词: sodium iodide symporter; autoimmune thyroiditis; autoimmune sialadenitis; Hashimoto's thyroiditis; Sjogren's syndrome

It is not known why about twenty percent of patients with Hashimoto's thyroiditis show the symptoms of Sjogren's syndrome, such as conjunctivitis and xerostomia. Sodium iodide symporter (NIS) expresses not only in thyroid gland but also in salivary gland. The purpose of this study is to examine the pathological role of NIS in autoimmune thyroiditis (Hashimoto's thyroiditis) and autoimmune sialadenitis (Sjogren's syndrome), especially in patients with both diseases. So I plan to examine whether the immunized mice with NIS show thyroiditis and/or sialadenitis or not. CBA/J mice were immunized with NIS expressing 293 cells with TiterMax Gold Adjuvant or Complete Freund's Adjuvant. In some mice, IL-12 was injected with NIS expressing cells to induce Th1 cytokines, which may enhance thyroiditis. Control mice were immunized with NIS non-expressing 293 cells. However the mice immunized with NIS expressing cells did not show lymphocyte infiltration in thyroid gland or salivary gland. Moreover anti-NIS antibody could not be detected in their sera by radioligand assay and iodide-uptake-inhibition assay. I conclude that the immunization with NIS expressing cells could not induce sufficient autoimmune reaction. Recently TSH receptor, which is a membrane protein like NIS, was reported to induce thyroiditis by genetic immunization. I plan to immunize mice with NIS by genetic immunization to induce thyroiditis and sialadenitis.

目前尚不清楚为什么大约20%的桥本甲状腺炎患者表现出干燥综合征的症状，如结膜炎和口干。钠碘转运体（NIS）不仅在甲状腺有表达，而且在唾液腺也有表达.本研究的目的是研究NIS在自身免疫性甲状腺炎（桥本甲状腺炎）和自身免疫性涎腺炎（干燥综合征）中的病理作用，特别是在这两种疾病的患者中。因此，我计划检查用NIS免疫的小鼠是否出现甲状腺炎和/或涎腺炎。CBA/J小鼠用表达NIS的293细胞与TiterMax Gold佐剂或完全弗氏佐剂免疫。在一些小鼠中，IL-12与NIS表达细胞一起注射以诱导Th 1细胞因子，这可能增强甲状腺炎。用NIS非表达293细胞免疫对照小鼠。而NIS表达细胞免疫小鼠后，甲状腺和唾液腺中未见淋巴细胞浸润。放射配体法和碘摄取抑制法均未检测到抗NIS抗体。结论：NIS表达细胞免疫不能诱导足够的自身免疫反应。近年来，TSH受体是一种类似NIS的膜蛋白，被报道可通过基因免疫诱导甲状腺炎。我计划用NIS基因免疫小鼠，诱发甲状腺炎和涎腺炎。

项目成果

Kiyoshi Watanabe: "Characteristics of experimental autoimmune hypophysitis in rats: major antigens are growth hormone, thyrotropin, and luteinizing hormone in this model"Autoimmunity. 33・4. 265-274 (2001)

Kiyoshi Watanabe：“大鼠实验性自身免疫性垂体炎的特征：该模型中的主要抗原是生长激素、促甲状腺激素和黄体生成素”33・4（2001）。

Kiyoshi Watanabe: "Characteristics of experimental autoimmune hypophysitis in rats : major antigens are growth hormone, thyrotropin, and lutenizing hormone in this model"Autoimmunity. 33・4. 265-274 (2001)

Kiyoshi Watanabe：“大鼠实验性自身免疫性垂体炎的特征：该模型中的主要抗原是生长激素、促甲状腺激素和促黄体激素”33・4（2001）。

Yoh Hidaka: "Increased serum concentration of eosinophil derived neurotoxin in patients with Graves' disease"Thyroid. in press. (2003)

Yoh Hidaka：“格雷夫斯病患者中嗜酸性粒细胞衍生的神经毒素的血清浓度增加”甲状腺。

Yuki Shimaoka: "Influence of breast-feeding on the production of cytokines"American Journal of Reproductive Immunology. 45・2. 100-102 (2001)

Yuki Shimaoka：“母乳喂养对细胞因子产生的影响”美国生殖免疫学杂志 45・2（2001）。

Taku Kashiwai: "Practical treatment with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves' disease"Endocrine Journal. 50・1. 45-49 (2003)

Taku Kashiwai：“用最小维持剂量的抗甲状腺药物预测格雷夫斯病的缓解”内分泌杂志 50・1（2003）。