Altered balance between self‐reactive T helper ( T h)17 cells and T h10 cells and between full‐length forkhead box protein 3 ( FoxP3) and FoxP3 splice variants in H ashimoto's thyroiditis

Summary T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin ( IL) ‐10‐producing T h10 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 forkhead box protein 3 ( FoxP3) compared to FoxP3Δ2 , missing exon 2. T h17 and T h10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self‐antigens to induce T h17 or T h10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with H ashimoto's thyroiditis ( HT ) or G raves' disease ( GD ) to polyclonal stimulation, or stimulation with human thyroglobulin ( TG ), human thyroid peroxidase ( TPO ), or Esherichia  coli lipopolysaccharide ( LPS ). TPO and LPS induced increased differentiation of naive CD4 + CD45RA + CD45R0 – T cells from HT patients into T h17 cells. T h10 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 show that an increased T h17 :  T h10 ratio was found in HT patients after stimulation with thyroid‐specific self‐antigens. We also observed an elevated baseline production of IL ‐6 and transforming growth factor ( TGF) ‐β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3 . This may contribute to the skewing towards T h17 cell responses in HT .