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

Autor: H. O. Madsen, B. Kristensen, Terry J. Smith, Laszlo Hegedüs, Claus Henrik Nielsen
Rok vydání: 2014
Předmět:
Lipopolysaccharides
Male
Iodide Peroxidase/immunology
Cellular differentiation
medicine.medical_treatment
Graves' disease
Stimulation
Autoantigens
Thyroiditis
Alternative Splicing/drug effects
Iron-Binding Proteins
Immunology and Allergy
Medicine
Protein Isoforms
Protein Isoforms/immunology
Graves Disease/immunology
Interleukin
FOXP3
hemic and immune systems
Cell Differentiation
Forkhead Transcription Factors
Regulatory T cells
Middle Aged
Thyroglobulin/immunology
Graves Disease
Interleukin-10
Female
Forkhead Transcription Factors/immunology
Adult
medicine.medical_specialty
Escherichia coli/chemistry
Immunology
Antigens
CD/immunology
Hashimoto Disease
Iodide Peroxidase
Thyroglobulin
Transforming Growth Factor beta1
Hashimoto's thyroiditis
Autoantigens/immunology
Antigens
CD
Internal medicine
Escherichia coli
Th17 Cells/immunology
Humans
Th17 cells
Transforming Growth Factor beta1/immunology
Aged
business.industry
Interleukin-6
Interleukins
Original Articles
medicine.disease
Iron-Binding Proteins/immunology
Alternative Splicing
Endocrinology
CTLA-4
Cell Differentiation/drug effects
Hashimoto Disease/immunology
Th17 Cells
Interleukin-6/immunology
Interleukin-10/immunology
business
Lipopolysaccharides/chemistry
Zdroj: Kristensen, B, Hegedüs, L, Smith, T J & Nielsen, C H 2015, ' 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 ', Clinical and Experimental Allergy, vol. 180, no. 1, pp. 58-69 . https://doi.org/10.1111/cei.12557
ISSN: 1365-2249
DOI: 10.1111/cei.12557
Popis: 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 Esherichia coli 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.
Databáze: OpenAIRE
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