Physiological low-dose oestrogen promotes the development of experimental autoimmune thyroiditis through the up-regulation of Th1/Th17 responses

J Reprod Immunol. 2018 Apr:126:23-31. doi: 10.1016/j.jri.2018.02.001. Epub 2018 Feb 7.

Abstract

Previous studies have reported a preponderance of autoimmune thyroiditis (AIT) in females, but the detailed mechanisms have not been elucidated. In this study, we explored the effects of oestrogen on experimental AIT (EAT) and its potential mechanisms in an ovariectomised mouse model through the supplementation of high (equivalent to the level during pregnancy) or low (equivalent to the level at the oestrus stage) doses of oestradiol (E2). We found that EAT incidence, the intrathyroidal inflammatory score, serum anti-thyroglobulin IgG2b levels, splenic mRNA expression of Th1- and Th17-specific transcription factors and typical cytokines and the proportion of IL-12-producing dendritic cells were significantly increased in EAT mice treated with low-dose E2 compared with those in the control group. However, they were not changed when administered with high-dose E2. These findings indicate that low physiological levels of E2 can stimulate the occurrence and development of EAT through the up-regulation of Th1/Th17 responses.

Keywords: Autoimmunity; Oestradiol; Th1; Th17; Thyroiditis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Estrogens / metabolism*
  • Humans
  • Immunization
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Mice
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Thyroid Gland / immunology*
  • Thyroiditis, Autoimmune / genetics
  • Thyroiditis, Autoimmune / metabolism*
  • Up-Regulation

Substances

  • Autoantibodies
  • Cytokines
  • Estrogens
  • anti-thyroglobulin