Prominent epigenetic and transcriptomic changes in CD4


Journal

Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974

Informations de publication

Date de publication:
27 Apr 2023
Historique:
received: 17 10 2022
accepted: 17 04 2023
medline: 1 5 2023
pubmed: 28 4 2023
entrez: 27 4 2023
Statut: epublish

Résumé

Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4 Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4 Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets. This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4

Sections du résumé

BACKGROUND BACKGROUND
Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4
METHODS METHODS
Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4
RESULTS RESULTS
Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets.
CONCLUSION CONCLUSIONS
This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4

Identifiants

pubmed: 37106402
doi: 10.1186/s12974-023-02781-2
pii: 10.1186/s12974-023-02781-2
pmc: PMC10134602
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

98

Subventions

Organisme : Neuroförbundet
ID : F2018-0052
Organisme : Forskningsrådet i Sydöstra Sverige
ID : FORSS-315121
Organisme : Stiftelsen för Strategisk Forskning
ID : SB16-0011
Organisme : Vetenskapsrådet
ID : 2018-02776

Informations de copyright

© 2023. The Author(s).

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Auteurs

Alberto Zenere (A)

Division of Automatic Control, Department of Electrical Engineering, Linköping University, Linköping, Sweden.

Sandra Hellberg (S)

Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden. sandra.hellberg@liu.se.

Georgia Papapavlou Lingehed (G)

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Maria Svenvik (M)

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Obstetrics and Gynecology, Region Kalmar County, Kalmar, Sweden.

Johan Mellergård (J)

Department of Neurology, Linköping University, Linköping, Sweden.
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Charlotte Dahle (C)

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.

Magnus Vrethem (M)

Department of Neurology, Linköping University, Linköping, Sweden.
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Johanna Raffetseder (J)

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Mohsen Khademi (M)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Tomas Olsson (T)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Marie Blomberg (M)

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Obstetrics and Gynecology, Linköping University, Linköping, Sweden.

Maria C Jenmalm (MC)

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Claudio Altafini (C)

Division of Automatic Control, Department of Electrical Engineering, Linköping University, Linköping, Sweden.

Mika Gustafsson (M)

Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden. mika.gustafsson@liu.se.

Jan Ernerudh (J)

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.

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