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

B Kristensen; Laszlo Hegedüs; H O Madsen; T J Smith; Claus Henrik Nielsen

doi:10.1111/cei.12557

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

B Kristensen, Laszlo Hegedüs, H O Madsen, T J Smith, Claus Henrik Nielsen

25 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Clinical and Experimental Immunology
Volume	180
Issue number	1
Pages (from-to)	58-69
Number of pages	12
ISSN	0009-9104
DOIs	https://doi.org/10.1111/cei.12557
Publication status	Published - 1 Apr 2015

Keywords

Adult
Aged
Alternative Splicing
Antigens, CD
Autoantigens
Cell Differentiation
Escherichia coli
Female
Forkhead Transcription Factors
Graves Disease
Hashimoto Disease
Humans
Interleukin-10
Interleukin-6
Iodide Peroxidase
Iron-Binding Proteins
Lipopolysaccharides
Male
Middle Aged
Protein Isoforms
Th17 Cells
Thyroglobulin
Transforming Growth Factor beta1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/cei.12557

cei.12557Final published version, 258 KB

Cite this

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. / Kristensen, B; Hegedüs, Laszlo; Madsen, H O et al.
In: Clinical and Experimental Immunology, Vol. 180, No. 1, 01.04.2015, p. 58-69.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{f471d70858c0437b8e0317525aed794d,

title = "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",

abstract = "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.",

keywords = "Adult, Aged, Alternative Splicing, Antigens, CD, Autoantigens, Cell Differentiation, Escherichia coli, Female, Forkhead Transcription Factors, Graves Disease, Hashimoto Disease, Humans, Interleukin-10, Interleukin-6, Iodide Peroxidase, Iron-Binding Proteins, Lipopolysaccharides, Male, Middle Aged, Protein Isoforms, Th17 Cells, Thyroglobulin, Transforming Growth Factor beta1",

author = "B Kristensen and Laszlo Heged{\"u}s and Madsen, {H O} and Smith, {T J} and Nielsen, {Claus Henrik}",

note = "{\textcopyright} 2014 British Society for Immunology.",

year = "2015",

month = apr,

day = "1",

doi = "10.1111/cei.12557",

language = "English",

volume = "180",

pages = "58--69",

journal = "Clinical and Experimental Immunology",

issn = "0009-9104",

publisher = "Wiley-Blackwell",

number = "1",

}

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

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 - 0009-9104

VL - 180

SP - 58

EP - 69

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this