Altered balance between self-reactive Th17 cells and Th10 cells and between full-length FOXP3 and FOXP3 splice variants in Hashimoto's thyroiditis

Birte Kristensen, Laszlo Hegedüs, Hans O Madsen, Terry J Smith, Claus H Nielsen

36 Citations (Scopus)

Abstract

Th17 cells play a pathogenic role in autoimmune disease, while IL-10-producing T-helper (Th10) cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact FOXP3 compared to FOXP3Δ2, missing exon 2. Th17- and Th10-cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17- or Th10-cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or E. coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naïve CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10-cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together our data shows an increased Th17: Th10 ratio was found in HT patients after stimulation with thyroid specific self-antigens. We also observed an elevated baseline production of IL-6 and TGF-β1 and of mRNA encoding FOXP3Δ2 rather than intact FOXP3. This may contribute to the skewing towards Th17-cell responses in HT.

Original languageEnglish
JournalClinical and Experimental Immunology
Volume180
Issue number1
Pages (from-to)58-69
ISSN0009-9104
DOIs
Publication statusPublished - 2015

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