The significance of immune-related molecule expression profiles in an animal model of Graves' disease.
BACKGROUND
The thyrotropin receptor (TSHR) A-subunit has been reported to be a critical autoantigen in the generation of thyroid-stimulating antibodies, thereby causing Graves' disease (GD). However, immune mechanisms associated with GD animal models induced by TSHR A-subunit are poorly understood until now.


METHODS
Female BALB/c mice (n = 23) were randomly divided into two groups, and GD presentation was monitored following injection with either 50 μl phosphate-buffered saline containing 10(9) particles of adenovirus expressing the human TSHR A-subunit (Ad-TSHR289) or the Ad-LacZ control. Expressions of CD40, CD40L, CD80, CD86, CD28, CTLA-4, FOXP3 and IL-17A in various tissues were assessed by quantitative RT-PCR and immunohistochemical assays.


RESULTS
Compared with control group, mice of the hyperthyroid group showed significant elevation of expression in the thyroid of CD40 and CD86, expression in the heart of CD28, CD40 and CD40L and expression in the liver of CD28, CD40 and CD86. Conversely, there was significantly diminished expression of CTLA-4 in the thymus of mice in the hyperthyroid group. Expression of all genes examined was not significantly different in the spleens of mice from either of the groups and CD40L and FOXP3 expression was not detected in the thyroids of hyperthyroid mice.


CONCLUSIONS
The expression profile of multiple immune-related molecules differed in mice in the GD group following Ad-TSHR289 immunization, suggesting that these molecules played a potential role in GD pathogenesis.
Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an 710061, P.R. China.
Feng
F
Ye
Peng
P
Hou
Xiaoyan
X
Wu
Xiaodan
X
Ma
Lei
L
Gao
Liping
L
Wu
Li
L
Xu
Bingyin
B
Shi
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013974:Thyroxine / Q000097:blood
D051940:B7-2 Antigen; D019013:CD40 Antigens; D011989:Receptors, Thyrotropin; D013974:Thyroxine