Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis

TY - JOUR

T1 - Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis

AU - Kristensen, B

AU - Hegedüs, Laszlo

AU - Madsen, H O

AU - Smith, T J

AU - Nielsen, Claus Henrik

N1 - © 2014 British Society for Immunology.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Summary: T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing 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 forkhead box protein 3 (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 Esherichiacoli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive 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 show that 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 transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT.

AB - Summary: T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing 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 forkhead box protein 3 (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 Esherichiacoli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive 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 show that 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 transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT.

KW - Adult

KW - Aged

KW - Alternative Splicing

KW - Antigens, CD

KW - Autoantigens

KW - Cell Differentiation

KW - Escherichia coli

KW - Female

KW - Forkhead Transcription Factors

KW - Graves Disease

KW - Hashimoto Disease

KW - Humans

KW - Interleukin-10

KW - Interleukin-6

KW - Iodide Peroxidase

KW - Iron-Binding Proteins

KW - Lipopolysaccharides

KW - Male

KW - Middle Aged

KW - Protein Isoforms

KW - Th17 Cells

KW - Thyroglobulin

KW - Transforming Growth Factor beta1

U2 - 10.1111/cei.12557

DO - 10.1111/cei.12557

M3 - Journal article

C2 - 25412700

SN - 0964-2536

VL - 180

SP - 58

EP - 69

JO - Clinical and Experimental Immunology, Supplement

JF - Clinical and Experimental Immunology, Supplement

IS - 1

ER -