Rapamycin restores CD4 + T cell subsets imbalance in Graves′ ophthalmopathy mice model
10.3760/cma.j.cn311282-20221223-00708
- VernacularTitle:雷帕霉素改善Graves眼病小鼠CD4 + T细胞亚群失衡的研究
- Author:
Meng ZHANG
1
;
Ling WANG
;
Xi DING
;
Mingqian HE
;
Ziyi CHEN
;
Xiaoyan WU
;
Liping WU
;
Bingyin SHI
;
Yue WANG
Author Information
1. 西安交通大学第一附属医院内分泌科，西安 710061
- Keywords:
Graves′ ophthalmopathy;
Rapamycin;
CD4 + T cell subsets;
Balb/c mice;
Animal model
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(11):964-973
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.
