Treg cells as a protective factor for Hashimoto`s thyroiditis: a Mendelian randomization study

Front Endocrinol (Lausanne). 2024 Mar 8:15:1347695. doi: 10.3389/fendo.2024.1347695. eCollection 2024.

Abstract

Background and objectives: Hashimoto's thyroiditis (HT), a chronic autoimmune disorder impacting thyroid function, is a growing public health concern. The relationship between Treg cells and HT has been extensively studied, with Treg cells considered crucial in suppressing HT progression. However, these studies have mainly been observational, limiting our understanding of Treg cells' impact on HT risk. Leveraging large datasets, we utilized Mendelian randomization (MR) analysis to examine the causal association between Treg cell biomarkers and HT, providing additional validation for these relationships.

Methods: Comprehensive two-sample Mendelian randomization analysis was performed to determine the causal association between Treg cells signatures and HT in this study. Based on publicly available genetic data, we explored causal associations between 165 Treg cells signatures and HT risk.

Results: The European cohort study has identified five Treg cell phenotypes that causally protect against HT risk. Resting Treg %CD4 (OR = 0.975, 95% CI = 0.954~0.998, P = 0.030); CD4 on resting Treg (OR = 0.938, 95% CI = 0.882~0.997, P = 0.041; CD28- CD8dim %CD8dim (OR = 0.983, 95% CI = 0.969~0.998, P = 0.030); CD25 on CD39+ resting Treg (OR = 0.926, 95% CI = 0.864~0.991, P = 0.026); 5) CD28 on activated & secreting Treg (OR = 0.969, 95% CI = 0.942~0.996, P = 0.025). The Asian cohort study has identified four Treg cell phenotypes negatively correlated with the risk of HT. CD25hi %T cell (OR = 0.635, 95% CI = 0.473~852, P = 0.002); CD4 Treg %CD4 (OR = 0.829, 95% CI = 0.687~1.000, P = 0.050); CD127-CD8br %T cell (OR = 0.463, 95% CI =0.311~0.687, P< 0.001); CD3 on resting Treg (OR = 0.786, 95% CI = 0.621~0.994, P = 0.044).

Conclusion: Our study has demonstrated the close connection between Treg cells and HT by genetic means, thus providing foundational basis for future research.

Keywords: Hashimoto`s thyroiditis; MR analysis; Treg cells; causal inference; immunity.

MeSH terms

  • CD28 Antigens
  • Cohort Studies
  • Hashimoto Disease* / genetics
  • Humans
  • Mendelian Randomization Analysis
  • Protective Factors
  • T-Lymphocytes, Regulatory*

Substances

  • CD28 Antigens

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The research was funded by the Henan science and technology research project (NO.222102310187), Key scientific research projects of universities of Henan Provincial Department of Education (No:21A360018), 2022 Provincial Science and Technology R&D Plan Joint Fund (cultivation of superior disciplines) (No: 222301420024).