Autoimmune thyroid diseases (AITD) are the most common autoimmune endocrine diseases. The major forms of AITD are Hashimoto's thyroiditis (HT), causing hypothyroidism, and Graves' disease (GD), causing hyperthyroidism. The hallmark of these conditions is thyroid dysfunction associated with the presence of lymphocytic infiltrates in the thyroid. Despite substantial clinical and experimental data supporting a role for 1vmphocvtes in triggering and sustaining AITD, factors responsible for their trafficking into the thyroid remain unknown. Our working hypothesis is that lymphocytes are recruited into the thyroid by a particular set of chemokines. Chemokine expression has been documented within the thyroid in different forms of AITD and we now provide direct evidence that their expression in transgenic mice is sufficient to induce lymphocytic infiltration of the thyroid. Animals expressing the chemokine CCL21 in the thyroid present a significant lymphocytic infiltrate that is organized into discrete T and B cell areas, resembling the infiltrates found in AITD. Together, these results strongly suggest that chemokines are key players in AITD. In this proposal we plan to investigate the role of chemokines in thyroid homeostasis and disease. Specifically we will:
AIM 1. Define the expression profile and function of chemokines in the thyroid during homeostasis and disease.
AIM 2. Determine the mechanisms underlying the lymphocytic infiltration promoted by CCL21 in the thyroid.
AIM 3. Determine if chemokine blockade will alter chemokine-induced leukocyte recruitment to the thyroid and interfere with the development of thyroid autoimmune disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK067989-03
Application #
7050585
Study Section
Endocrinology Study Section (END)
Program Officer
Spain, Lisa M
Project Start
2004-07-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$364,137
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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