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T cells are influen...
T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus
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- Houtman, Miranda (author)
- Karolinska Institutet
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- Shchetynsky, Klementy (author)
- Karolinska Institutet
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- Chemin, Karine (author)
- Karolinska Institutet
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- Hensvold, Aase Haj (author)
- Karolinska Institutet
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- Ramsköld, Daniel (author)
- Karolinska Institutet
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- Tandre, Karolina (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Eloranta, Maija-Leena (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Uebe, Steffen (author)
- Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany
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- Catrina, Anca Irinel (author)
- Karolinska Institutet
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- Malmström, Vivianne (author)
- Karolinska Institutet
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- Padyukov, Leonid (author)
- Karolinska Institutet
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(creator_code:org_t)
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2018
- 2018
- English.
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In: Journal of Autoimmunity. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0896-8411 .- 1095-9157. ; 90, s. 28-38
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Abstract
Subject headings
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- Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, type I diabetes, and inflammatory bowel disease. However, the functional consequences of these SNPs are poorly characterized. Herein, we show in blood cells that SNPs in the PTPN2 locus are highly correlated with DNA methylation levels at four CpG sites downstream of PTPN2 and expression levels of the long non-coding RNA (IncRNA) LINC01882 downstream of these CpG sites. We observed that LINC01882 is mainly expressed in T cells and that anti-CD3/CD28 activated naive CD4(+) T cells downregulate the expression of LINC01882. RNA sequencing analysis of LINC01882 knockdown in Jurkat T cells, using a combination of antisense oligo-nucleotides and RNA interference, revealed the upregulation of the transcription factor ZEB1 and kinase MAP2K4, both involved in IL-2 regulation. Overall, our data suggests the involvement of LINC01882 in T cell activation and hints towards an auxiliary role of these non-coding SNPs in autoimmunity associated with the PTPN2 locus.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- RA
- Genome-wide association
- methQTL
- eQTL
- Long non-coding RNA
- T cell
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Houtman, Miranda
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Shchetynsky, Kle ...
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Chemin, Karine
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Hensvold, Aase H ...
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Ramsköld, Daniel
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Tandre, Karolina
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show more...
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Eloranta, Maija- ...
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Rönnblom, Lars
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Uebe, Steffen
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Catrina, Anca Ir ...
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Malmström, Vivia ...
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Padyukov, Leonid
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Journal of Autoi ...
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Uppsala University
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Karolinska Institutet