A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21.
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-alpha 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.
Martin
Andrea P
AP
Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Coronel
Elizabeth C
EC
Sano
Gen-ichiro
G
Chen
Shu-Cheng
SC
Vassileva
Galya
G
Canasto-Chibuque
Claudia
C
Sedgwick
Jonathon D
JD
Frenette
Paul S
PS
Lipp
Martin
M
Furtado
Glaucia C
GC
Lira
Sergio A
SA
D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology*; D005260:Female; D019041:L-Selectin / Q000032:analysis; D008214:Lymphocytes / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D051381:Rats; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000502:physiology; D013959:Thyroid Diseases / Q000209:etiology; D013961:Thyroid Gland / Q000473:pathology*
C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; C515372:Ccr7 protein, rat; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008233:Lymphotoxin-alpha; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin