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

Andrea P. Martin, Elizabeth C. Coronel, Gen Ichiro Sano, Shu Cheng Chen, Galya Vassileva, Claudia Canasto-Chibuque, Jonathon D. Sedgwick, Paul S. Frenette, Martin Lipp, Glaucia C. Furtado, Sergio A. Lira

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

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 trafficking, 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-α 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.

Original languageEnglish (US)
Pages (from-to)4791-4798
Number of pages8
JournalJournal of Immunology
Volume173
Issue number8
StatePublished - Oct 15 2004
Externally publishedYes

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Chemokine CCL21
CC Chemokines
Thyroid Gland
Lymphocytes
Thyroid Diseases
Autoimmune Diseases
Transgenic Mice
L-Selectin
Lymphotoxin-alpha
Germinal Center
Venules
Thyroglobulin
B-Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Martin, A. P., Coronel, E. C., Sano, G. I., Chen, S. C., Vassileva, G., Canasto-Chibuque, C., ... Lira, S. A. (2004). A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21. Journal of Immunology, 173(8), 4791-4798.

A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21. / Martin, Andrea P.; Coronel, Elizabeth C.; Sano, Gen Ichiro; Chen, Shu Cheng; Vassileva, Galya; Canasto-Chibuque, Claudia; Sedgwick, Jonathon D.; Frenette, Paul S.; Lipp, Martin; Furtado, Glaucia C.; Lira, Sergio A.

In: Journal of Immunology, Vol. 173, No. 8, 15.10.2004, p. 4791-4798.

Research output: Contribution to journalArticle

Martin, AP, Coronel, EC, Sano, GI, Chen, SC, Vassileva, G, Canasto-Chibuque, C, Sedgwick, JD, Frenette, PS, Lipp, M, Furtado, GC & Lira, SA 2004, 'A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21', Journal of Immunology, vol. 173, no. 8, pp. 4791-4798.
Martin AP, Coronel EC, Sano GI, Chen SC, Vassileva G, Canasto-Chibuque C et al. A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21. Journal of Immunology. 2004 Oct 15;173(8):4791-4798.
Martin, Andrea P. ; Coronel, Elizabeth C. ; Sano, Gen Ichiro ; Chen, Shu Cheng ; Vassileva, Galya ; Canasto-Chibuque, Claudia ; Sedgwick, Jonathon D. ; Frenette, Paul S. ; Lipp, Martin ; Furtado, Glaucia C. ; Lira, Sergio A. / A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21. In: Journal of Immunology. 2004 ; Vol. 173, No. 8. pp. 4791-4798.
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abstract = "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 trafficking, 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-α 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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N2 - 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 trafficking, 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-α 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.

AB - 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 trafficking, 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-α 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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