The role of chemokines in experimental thyroiditis

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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.