Title:Effect of Halofuginone on the Pathogenesis of Autoimmune Thyroid Disease in Different Mice Models
Volume: 17
Issue: 2
Author(s): Xin Hou, Jin Zhou, Rong Yang, Shanshan Liu, Mei Bi, Tong Liu, Chenling Fan, Haixia Guan, Weiping Teng, Zhongyan Shan and Yushu Li*
Affiliation:
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University; Institute of Endocrinology, The Liaoning Provincial Key Laboratory of Endocrine Diseases, China Medical University, 155 Nanjing Bei Street, Liaoning, Shenyang 110001,China
Keywords:
Halofuginone, graves' disease, autoimmune thyroiditis, animal experiment, lymphocytes, mice.
Abstract: Objective: Our objectives were to investigate the therapeutic effect of halofuginone (HF)
in the treatment of autoimmune thyroid diseases (AITDs) and explore its underlying mechanism of
action.
Methods: The Graves' disease (GD) model was generated by immunizing female BALB/c mice with
adenovirus expressing the TSH receptor A subunit (Ad-TSHR289). The Ad-TSHRA+HF and Ad-
TSHRA+DMSO groups were injected intraperitoneally with HF or the vehicle control (DMSO),
respectively. The autoimmune thyroiditis (AIT) group consisted of female NOD.H-2h4 mice that
were administered NaI in the drinking water and intraperitoneally injected daily with the vehicle
control (DMSO) during the study period. The AIT/HF group consisted of female NOD.H-2h4 mice
that were administered NaI in the drinking water and intraperitoneally injected daily with HF. The
frequencies of splenic Th17 cells, Tregs and Bregs were determined by flow cytometry. The mRNA
levels of IL-17, forkhead box P3 (Foxp3), RORγt and IL-10 were determined by real-time PCR.
Results: In both Ad-TSHRA+DMSO and Ad-TSHRA+HF groups, 10 out of 15 mice displayed serum
T4 and TSAb levels above 3 SD beyond the mean control levels. The number of
CD4+CD25+Foxp3+ T lymphocytes in the GD model was significantly increased in the HF group
compared with the DMSO group (P < 0.05). The mRNA level of Foxp3 was significantly increased
in the Ad-TSHRA+HF group compared with the Ad-TSHRA+DMSO group (P < 0.05). However,
neither the abundance of CD4+IL-17+ T cell subpopulation nor the mRNA expression level of RORγt
differed significantly between the Ad-TSHRA+HF and Ad-TSHRA+DMSO groups (P > 0.05). The
serum TgAb titer was significantly reduced in the AIT/HF group compared with the AIT group
(P < 0.01). The differences in the number of CD4+CD25+Foxp3+ T lymphocytes and the mRNA
levels of Foxp3 between the AIT/HF and AITgroups were not significant (P > 0.05). However,
the number of CD4+IL-17+ T cells and the mRNA levels of IL-17 and RORγt were significantly
increased in HF-treated mice compared with the non-treated AIT-induced mice (P < 0.05).
Conclusion: Treatment with HF significantly decreased the incidence of AIT by decreasing the
number of CD4+IL-17+ T cells.
