CCR7 deficiency in NOD mice leads to thyroiditis and primary hypothyroidism.
CCR7 is involved in the initiation of immune responses and has been recently implicated in the control of tolerance. To analyze the role of CCR7 in autoimmunity, we backcrossed CCR7(ko/ko) mice (in which ko signifies deficient) onto the autoimmune-prone NOD background. Surprisingly, NODCCR7(ko/ko) mice never developed diabetes, but showed severe inflammation in multiple tissues including thyroid, lung, stomach, intestine, uterus, and testis. NODCCR7(ko/ko) mice had a marked enlargement of the thyroid gland (goiter) that was associated with circulating autoantibodies against thyroglobulin, and development of primary hypothyroidism (decreased levels of serum thyroxin, and augmented levels of thyroid-stimulating hormone in the pituitary gland), features found in Hashimoto's thyroiditis. Cells isolated from diseased thyroids and activated splenocytes from NODCCR7(ko/ko) animals induced goiter in NOD.SCID recipients, demonstrating that autoreactive cells were generated in the absence of CCR7. Moreover, thyroid disease could be accelerated in young NODCCR7(ko/ko) mice by immunization with thyroglobulin. These results demonstrate the complexity in the generation of multiple autoimmune phenotypes in NOD mice and indicate that CCR7 is a key molecule in their development.
Martin
Andrea P
AP
Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Marinkovic
Tatjana
T
Canasto-Chibuque
Claudia
C
Latif
Rauf
R
Unkeless
Jay C
JC
Davies
Terry F
TF
Takahama
Yousuke
Y
Furtado
Glaucia C
GC
Lira
Sergio A
SA
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D007037:Hypothyroidism / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D054400:Receptors, CCR7 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7