The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis

Immunol Invest. 2022 Jul;51(5):1170-1181. doi: 10.1080/08820139.2021.1915329. Epub 2021 Apr 26.

Abstract

The ratio of T helper (Th) 17 and T regulatory (Treg) cells in patients with polycystic ovary syndrome complicated with autoimmune thyroiditis (PCOS-AIT) remains unreported. The study aimed to determine the Th17/Treg cell paradigm in PCOS-AIT patients. In peripheral blood mononuclear cells from PCOS patients and controls, the percentages of Th17 and Treg cells were measured by flow cytometry, the mRNA levels of a Th17-related transcription factor (ROR-γt) and a Treg-specific transcription factor (Foxp3) were determined by qRT-PCR, and the levels of Th17-related cytokines and Treg-related cytokines were measured by ELISA. Additionally, to examine the effect of testosterone on the Th17/Treg cell balance in vitro, cultured PCOS-AIT CD4+ T cells were treated with 10 μM testosterone for 24 h, and the Th17/Treg cell proportions and expression of Th17/Treg cell-associated transcription factors and cytokines were analyzed by flow cytometry, qRT-PCR, and ELISA. The Th17 cell percentage, Th17/Treg cell ratio, and expression of Th17-related ROR-γt and IL-17 were significantly higher in peripheral blood mononuclear cells from PCOS-AIT patients than in those from controls. In CD4+ T cells derived from PCOS-AIT patients, testosterone significantly decreased the Th17 cell percentage, Th17/Treg ratio, mRNA level of ROR-γt, and production of Th17-related cytokines and increased the Treg cell percentage, mRNA level of Foxp3, and secretion of Treg-related cytokines. The Th17/Treg cell imbalance favoring proinflammatory Th17 cells is involved in the pathogenesis of PCOS-AIT. Targeting the Th17/Treg cell axis may have therapeutic potential in the treatment of PCOS-AIT.

Keywords: Polycystic ovary syndrome; Th17; Treg; autoimmune thyroiditis; testosterone.

MeSH terms

  • Cytokines / metabolism
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Hashimoto Disease* / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Polycystic Ovary Syndrome* / metabolism
  • RNA, Messenger
  • T-Lymphocytes, Regulatory
  • Testosterone / metabolism
  • Th17 Cells
  • Thyroiditis, Autoimmune*

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • Testosterone