Tissue Infiltrating LTi-Like Group 3 Innate Lymphoid Cells and T Follicular Helper Cells in Graves' and Hashimoto's Thyroiditis

Front Immunol. 2020 Apr 9:11:601. doi: 10.3389/fimmu.2020.00601. eCollection 2020.


Background: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid disorders (AITDs). These conditions have been associated to abnormalities in circulating regulatory T cells (Tregs). We postulated that immune perturbations could be more pronounced at the thyroid tissue level. Methods: The phenotype of PBMCs and immune cells infiltrating thyroid tissue from 19 patients with HT, 21 patients with GD, and 30 controls has been analyzed by flow cytometry. Results: We report that blood and thyroid Treg cell subsets are similarly represented in all AITDs patients and controls. Increased Lymphoid tissue inducer (LTi)-like ILC3 and CXCR5+ PD-1hi CD4+ T follicular helper cells (Tfh) tissue-infiltrating cells, together with the prevalence of tertiary lymphoid structures (TLS) and germinal centers (GCs) represented a typical immune signature in all HT and 60% of GD patients. In the remaining group of GD patients, the absence of the aforementioned abnormalities was associated with a higher prevalence of ophthalmopathy. Conclusion: Tissue infiltrating Lymphoid Tissue inducer-like group 3 Innate Lymphoid cells and T follicular helper cells are increased in most thyroid autoimmune disease.

Keywords: Graves' disease; Hashimoto's thyroiditis; follicular helper T cells; lymphoid tissue–inducer-like cells; regulatory T cells; thyroid autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / analysis
  • Graves Disease / immunology*
  • Hashimoto Disease / immunology*
  • Humans
  • Immunity, Innate*
  • Lymphocytes / immunology*
  • Lymphoid Tissue / immunology*
  • Male
  • Middle Aged
  • Receptors, CXCR5 / analysis
  • T Follicular Helper Cells / immunology*
  • T-Lymphocytes, Regulatory / immunology


  • CXCR5 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, CXCR5