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Sökning: id:"swepub:oai:DiVA.org:uu-468100" > Genomic Multiple Sc...

Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells

Mena, Jorge (författare)
Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain.
Alloza, Iraide (författare)
Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain.
Tulloch Navarro, Raquel (författare)
Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain.
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Aldekoa, Ane (författare)
Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain.
Diez Garcia, Javier (författare)
Biocruces Bizkaia Hlth Res Inst, Microscopy Facil, Baracaldo, Spain.
Villanueva Etxebarria, Ane (författare)
Kronikgune Inst Hlth Serv Res, Baracaldo, Spain.;Hlth Serv Res Network Chron Dis Red Invest Serv R, Bizkaia, Spain.;Galdakao Univ Hosp, Osakidetza Basque Hlth Serv, Res Unit, Galdakao, Spain.
Lindskog, Cecilia (författare)
Uppsala universitet,Klinisk och experimentell patologi
Antiguedad, Alfredo (författare)
Cruces Univ Hosp, Bizkaia Hlth Res Inst, Osakidetza Basque Hlth Serv, Dept Neurol, Baracaldo, Spain.
Boyero, Sabas (författare)
Cruces Univ Hosp, Bizkaia Hlth Res Inst, Osakidetza Basque Hlth Serv, Dept Neurol, Baracaldo, Spain.
Mendibe-Bilbao, Maria del Mar (författare)
Cruces Univ Hosp, Bizkaia Hlth Res Inst, Osakidetza Basque Hlth Serv, Dept Neurol, Baracaldo, Spain.
Alvarez de Arcaya, Amaya (författare)
Txagorritxu Univ Hosp, Dept Neurol, Osakidetza Basque Hlth Serv, Bioaraba Hlth Res Inst, Vitoria, Spain.
Sanchez Menoyo, Jose Luis (författare)
Galdakao Usansolo Univ Hosp, Biocruces Bizkaia Hlth Res Inst, Dept Neurol, Osakidetza Basque Hlth Serv, Galdakao, Spain.
Midaglia, Luciana (författare)
Univ Autonoma Barcelona, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Hosp Univ Hebron, Barcelona, Spain.
Villarrubia, Noelia (författare)
Red Espanola Esclerosis Multiple, Dept Immunol, Hosp Univ Ramo Y Cajal, Inst Ramo & Cajal Invest Invest Sanitaria IRYCIS, Madrid, Spain.
Malhotra, Sunny (författare)
Univ Autonoma Barcelona, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Hosp Univ Hebron, Barcelona, Spain.
Montalban, Xavier (författare)
Univ Autonoma Barcelona, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Hosp Univ Hebron, Barcelona, Spain.
Villar, Luisa Maria (författare)
Red Espanola Esclerosis Multiple, Dept Immunol, Hosp Univ Ramo Y Cajal, Inst Ramo & Cajal Invest Invest Sanitaria IRYCIS, Madrid, Spain.
Comabella, Manuel (författare)
Univ Autonoma Barcelona, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Hosp Univ Hebron, Barcelona, Spain.
Vandenbroeck, Koen (författare)
Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain.;Univ Pais Vasco UPV EHU, Dept Biochem & Mol Biol, Leioa, Spain.;Basque Fdn Sci, Ikerbasque, Bilbao, Spain.
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Biocruces Bizkaia Hlth Res Inst, Inflammat & Biomarkers Grp, Baracaldo, Spain Biocruces Bizkaia Hlth Res Inst, Microscopy Facil, Baracaldo, Spain. (creator_code:org_t)
2022-01-17
2022
Engelska.
Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
Relaterad länk:
https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
https://www.frontier...
https://urn.kb.se/re...
https://doi.org/10.3...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Intronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4(+) T lymphocytes of healthy controls. The biological function of ANKRD55, its role in the immune system, and cellular sources of expression other than lymphocytes remain uncharacterized. Here, we show that monocytes gain capacity to express ANKRD55 during differentiation in immature monocyte-derived dendritic cells (moDCs) in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). ANKRD55 expression levels are further enhanced by retinoic acid agonist AM580 but downregulated following maturation with interferon (IFN)-gamma and lipopolysaccharide (LPS). ANKRD55 was detected in the nucleus of moDC in nuclear speckles. We also analyzed the adjacent IL6ST, IL31RA, and SLC38A9 genes. Of note, in healthy controls, MS risk SNP genotype influenced ANKRD55 and IL6ST expression in immature moDC in opposite directions to that in CD4(+) T cells. This effect was stronger for a partially correlated SNP, rs13186299, that is located, similar to the main MS risk SNPs, in an ANKRD55 intron. Upon analysis in MS patients, the main GWAS MS risk SNP rs7731626 was associated with ANKRD55 expression levels in CD4(+) T cells. MoDC-specific ANKRD55 and IL6ST mRNA levels showed significant differences according to the clinical form of the disease, but, in contrast to healthy controls, were not influenced by genotype. We also measured serum sgp130 levels, which were found to be higher in homozygotes of the protective allele of rs7731626. Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo-DC) differentiation as a process potentially influenced by MS risk SNPs.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

ANKRD55
IL6ST
sgp130
multiple sclerosis
autoimmune

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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