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Epigenetic profiling in CD4+and CD8+T cells from Graves' disease patients reveals changes in genes associated with T cell receptor signaling
Inst Biomed & Translat Med, Mol Pathol, Tartu, Estonia..
Inst Biomed & Translat Med, Mol Pathol, Tartu, Estonia..
Inst Biomed & Translat Med, Mol Pathol, Tartu, Estonia..
Inst Biomed & Translat Med, Mol Pathol, Tartu, Estonia..
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2016 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 67, 46-56 p.Article in journal (Refereed) Published
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Abstract [en]

In Graves' disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with decreased levels of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients.

Place, publisher, year, edition, pages
2016. Vol. 67, 46-56 p.
Keyword [en]
Graves' disease, DNA methylation, Epigenetics, T cell signaling, TSHR
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-282328DOI: 10.1016/j.jaut.2015.09.006ISI: 000370884900006PubMedID: 26459776OAI: oai:DiVA.org:uu-282328DiVA: diva2:916832
Funder
EU, European Research Council, 262055 (ESGI)EU, European Research Council
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved

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Axelsson, TomasSyvänen, Ann-Christine

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