title: CCR7 deficiency in NOD mice leads to thyroiditis and primary hypothyroidism.
abstract: 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.
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Martin
authors.forename: Tatjana
authors.initials: T
authors.lastname: Marinkovic
authors.forename: Claudia
authors.initials: C
authors.lastname: Canasto-Chibuque
authors.forename: Rauf
authors.initials: R
authors.lastname: Latif
authors.forename: Jay C
authors.initials: JC
authors.lastname: Unkeless
authors.forename: Terry F
authors.initials: TF
authors.lastname: Davies
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.forename: Glaucia C
authors.initials: GC
authors.lastname: Furtado
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
mesh_terms: 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
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7