Low regulatory T cell and high IL-17 mRNA expression in a mouse Graves' disease model.
OBJECTIVE
Graves' disease (GD) is an autoimmune thyroid disease, and the most important characteristic of it is the presence of the thyroid-stimulating antibody (TSAb). The mechanisms of the TSAb elevation are still uncertain. Recent studies have suggested that the dysregulation of regulatory T cell (Treg) and T helper 17 (Th17) might stimulate the production of TSAb and be a pathogenesis of GD. However, the role of Treg and Th17 cells in the pathogenesis of GD is still debated. Our aim is to assess changes of Treg and Th17 cells in the spleen of a mouse in an in vivo GD model and try to explain the pathogenesis of GD.


METHODS
We used an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289) to immunise mice in order to induce GD in the model. Flow cytometry was used to measure the frequencies of splenic Treg and Th17 cells and real-time PCR to analyse the mRNA expression of forkhead box P3(Foxp3) and interleukin-17(IL-17).


RESULTS
Compared with the Ad-Control group, the frequencies of CD4+CD25+Foxp3+Treg cells were significantly decreased (p = 0.007) and gene expression of Foxp3 was down-regulated (p = 0.001) in the Ad-TSHR289 group. Though there was no significant difference in CD4+IL-17+T cell subpopulation between the two groups (p = 0.336), the IL-17 mRNA expression was significantly up-regulated in the Ad-TSHR289 group (p = 0.001).


CONCLUSIONS
The pathogenesis of GD may be associated with reduced Treg cells and increased IL-17 gene expression. The increased IL-17 mRNA needs to be explained by other mechanisms but not Th17 cells.
Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Chaoyang District, Beijing, 100029, China.|Department of Laboratory of Diabetes, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing, 100053, China.
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Yuan
Department of Laboratory of Diabetes, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing, 100053, China.
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Zhao
Department of Laboratory of Diabetes, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing, 100053, China.
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Zhu
Department of Laboratory of Diabetes, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing, 100053, China. yuanquanbeizhongyi@163.com.
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Liu
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D018828:Immunoglobulins, Thyroid-Stimulating; D020381:Interleukin-17; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin
Graves’ disease; IL-17; Th17; Treg