A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21

被引:72
作者
Martin, AP
Coronel, EC
Sano, G
Chen, SC
Vassileva, G
Canasto-Chibuque, C
Sedgwick, JD
Frenette, PS
Lipp, M
Furtado, GC
Lira, SA
机构
[1] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA
[2] Schering Plough Res Inst, Kenilworth, NJ 07033 USA
[3] DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA
[4] Max Delbruck Ctr Mol Med, Berlin, Germany
关键词
D O I
10.4049/jimmunol.173.8.4791
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lymphocytic infiltrates and lymphoid follicles with germinal centers are often detected in autoimmune thyroid disease (AITD), but the mechanisms underlying lymphocyte entry and organization in the thyroid remain unknown. We tested the hypothesis that CCL21, a chemokine that regulates homeostatic lymphocyte tracking, and whose expression has been detected in AITD, is involved in the migration of lymphocytes to the thyroid. We show that transgenic mice expressing CCL21 from the thyroglobulin promoter (TGCCL21 mice) have significant lymphocytic infiltrates, which are topologically segregated into B and T cell areas. Although high endothelial venules expressing peripheral lymph node addressin were frequently observed in the thyroid tissue, lymphocyte recruitment was independent of L-selectin or lymphotoxin-a but required CCR7 expression. Taken together, these results indicate that CCL21 is sufficient to drive lymphocyte recruitment to the thyroid, suggest that CCL21 is involved in AITD pathogenesis, and establish TGCCL21 transgenic mice as a novel model to study the formation and function of lymphoid follicles in the thyroid.
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页码:4791 / 4798
页数:8
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