The role of chemokines in experimental thyroiditis

描述（由申请人提供）：可靠的实验数据将人类自身免疫性甲状腺疾病（AITD）与趋化因子的表达联系起来，但迄今为止的研究大多是描述性的。我们已经开发了转基因模型来研究趋化因子在AITD中的作用。我们已经报道了在AITD中表达的趋化因子CCL 21的表达导致淋巴细胞和树突状细胞（DC）募集到甲状腺中。如在AITD中所发现的，淋巴细胞以类似淋巴滤泡的结构组织，其中存在血管结构如高内皮小静脉（HEV）和微血管。CCL 21的受体CCR 7在自身免疫易感NOD背景中的缺失有利于甲状腺炎的发展，表明CCL 21在AITD中的调节作用。我们的具体目标是：1）确定有利于甲状腺淋巴滤泡形成的机制，以及它们与EAT发展的相关性; 2）确定有利于NODCCR 7 ko/ko小鼠甲状腺炎发展的机制。许多类型的甲状腺疾病是由免疫系统细胞破坏甲状腺细胞引起的。 公共卫生相关性：我们将研究这些免疫细胞到达甲状腺的机制，并确定阻断其中一些机制是否会改变甲状腺疾病。这项工作应确定免疫成分在甲状腺疾病发病机制中的作用。

DESCRIPTION (provided by applicant): Solid experimental data links human autoimmune thyroid disease (AITD) and expression of chemokines, but the studies to date have been mostly descriptive. We have developed transgenic models to investigate the role of chemokines in AITD. We have reported that expression of CCL21, a chemokine expressed in AITD, leads to recruitment of lymphocytes and dendritic cells (DC) into the thyroid. As is found in AITD, lymphocytes organize in structures resembling lymphoid follicles, in which vascular structures such as high endothelial venules (HEV) and lymphatics are present. Deletion of CCR7, the receptor for CCL21, in the autoimmune-prone NOD background favors development of thyroiditis, suggesting a regulatory role for CCL21 in AITD. Our specific aims in this proposal are: 1) to define the mechanisms favoring the formation of thyroid lymphoid follicles, and their relevance to development of EAT; and 2), to define the mechanisms favoring development of thyroiditis in NODCCR7ko/ko mice. Many types of thyroid diseases are caused by destruction of the cells of the thyroid by cells of the immune system. PUBLLIC HEALTH RELEVANCE: We will investigate the mechanisms whereby these immune cells arrive in the thyroid and will determine if blocking some of these mechanisms will alter thyroid disease. This work should define the role of immune components in the pathogenesis of thyroid diseases.