Hypomethylation of miR-17-92 cluster in lupus T cells and no significant role for genetic factors in the lupus-associated DNA methylation signature.

CD4-Positive T-Lymphocytes / metabolism DNA Methylation / genetics Epigenesis, Genetic / genetics Epigenomics Humans Interferons / genetics Lupus Erythematosus, Systemic / genetics MicroRNAs / genetics T-Lymphocytes
autoimmunity lupus erythematosus, systemic polymorphism, genetic

Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
10 2022
Historique:
received: 13 04 2022
accepted: 07 06 2022
pubmed: 17 6 2022
medline: 15 9 2022
entrez: 16 6 2022
Statut: ppublish

Résumé

Lupus T cells demonstrate aberrant DNA methylation patterns dominated by hypomethylation of interferon-regulated genes. The objective of this study was to identify additional lupus-associated DNA methylation changes and determine the genetic contribution to epigenetic changes characteristic of lupus. Genome-wide DNA methylation was assessed in naïve CD4 In addition to the previously reported epigenetic signature in interferon-regulated genes, we observed hypomethylation in the promoter region of the miR-17-92 cluster in patients with lupus. Members of this microRNA cluster play an important role in regulating T cell proliferation and differentiation. Expression of two microRNAs in this cluster, miR-19b1 and miR-18a, showed a significant positive correlation with lupus disease activity. Among miR-18a target genes, The lupus defining epigenetic signature, characterised by robust hypomethylation of interferon-regulated genes, does not appear to be determined by genetic factors. Hypomethylation of the miR-17-92 cluster that plays an important role in T cell activation is a novel epigenetic locus for lupus.

Identifiants

DOI: 10.1136/annrheumdis-2022-222656 PMID: 35710306 PMC: PMC10259175
pubmed: 35710306
pii: annrheumdis-2022-222656
doi: 10.1136/annrheumdis-2022-222656
pmc: PMC10259175
mid: NIHMS1901924
doi:

Substances chimiques

MIRN17 microRNA, human 0
MicroRNAs 0
Interferons 9008-11-1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1428-1437

Subventions

Organisme : NIA NIH HHS
ID : P30 AG050911
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI097134
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103636
Pays : United States

Informations de copyright

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Patrick Coit (P)

Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, USA.

Xiavan Roopnarinesingh (X)

Graduate Program, Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

Lourdes Ortiz-Fernández (L)

Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Kathleen McKinnon-Maksimowicz (K)

Division of Rheumatology, Henry Ford Health System, Detroit, Michigan, USA.

Emily E Lewis (EE)

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Joan T Merrill (JT)

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

W Joseph McCune (WJ)

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Jonathan D Wren (JD)

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Amr H Sawalha (AH)

Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA asawalha@pitt.edu.
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
ORCID: 0000-0002-3884-962X

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Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD4+ › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Lupus érythémateux disséminé › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Hypomethylation of miR-17-92 cluster in lupus...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Hypomethylation of miR-17-92 cluster in lupus...