骨桥蛋白在Graves'病甲亢中致病机制的研究

Graves' Disease(GD) is a common autoimmune endocrine diseases which is mainly caused by the rise of thyroid-stimulating hormone receptor antibodies(TRAb) .The main treatment of Graves' Disease is using antithyroid drugs which have a long course and higher recurrence rate.In order to improve the treatment way to shorten the course , we have to study the immunity mechanism of TRAb produce.Osteopontin (OPN) is a pleiotropic extracellular matrix protein which acts as chemokine, cytokine and integrin and plays an important role in various autoimmune diseases.But we poorly know about the pathogenesis of OPN in GD. Our reserch team has found that Osteopontin(OPN) levels of GD patients are significantly high and there are a positive relationship with TRAb levels, however we have to further study the immunoregulation effect of OPN on immunocytes and thyroid follicular cells. According to the results of previous trials, our team chooses OPN as the entry point and focuses on researching the effect of OPN on the production of chemokines in thyroid follicular cells and the activation of immunocytes to clarify the effect of OPN on the pathogenesis of GD, find effective intervention targets and provide theoretical basises for shorten the course of Graves' Disease.

Graves'病甲亢（GD）是一种常见的自身免疫性内分泌疾病，是由于促甲状腺激素受体自身抗体（TRAb）升高所致，其主要治疗方法- - 抗甲状腺药物(ATD)疗程长，复发率较高。要改善治疗方法、缩短疗程，就必须深入研究导致TRAb产生的免疫机制。 骨桥蛋白（ OPN）是一种具有趋化、促炎性因子分泌和整合素性能的多功能胞外基质蛋白，与多种自身免疫性疾病发病密切相关，但在GD中的致病作用和机制却从未涉及。本课题组首次发现 GD患者血清中OPN明显升高，且与TRAb水平存在正相关关系，但OPN具体的免疫调节机制及其与免疫细胞和甲状腺细胞间的相互关系需进一步深入研究，因此本课题组拟以OPN为切入点，着重研究OPN在免疫细胞DC细胞、CD4+T细胞活化、增殖以及甲状腺滤泡细胞合成趋化因子中的作用，从而阐明OPN在GD中发病机制，并针对关键的靶点实施药物干预，为缩短Graves'病的病程提供理论依据。

Graves’病甲亢（GD）是一种常见的自身免疫性内分泌疾病，是由于促甲状腺激素受体自身抗体（TRAb）升高所致， 目前TRAb产生的免疫机制尚不明确。 骨桥蛋白（OPN）是一种具有趋化、促炎性因子分泌和整合素性能的多功能胞外基质蛋白。本课题在前期工作基础上发现OPN可通过上调CD40L表达促进自身抗体表达；还可通过促进CCL20的表达参与GD发病；GD患者血浆CCL21水平的升高受骨桥蛋白（OPN）调控。此外，在甲状腺局部OPN表达升高，可拮抗干扰素-γ诱导的甲状腺细胞趋化因子CXCL9分泌。本研究阐述了OPN在GD中的作用机制，可能可以作为GD诊断和治疗的新靶点。