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Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls.
Zenere, Alberto; Hellberg, Sandra; Papapavlou Lingehed, Georgia; Svenvik, Maria; Mellergård, Johan; Dahle, Charlotte; Vrethem, Magnus; Raffetseder, Johanna; Khademi, Mohsen; Olsson, Tomas; Blomberg, Marie; Jenmalm, Maria C; Altafini, Claudio; Gustafsson, Mika; Ernerudh, Jan.
Afiliación
  • Zenere A; Division of Automatic Control, Department of Electrical Engineering, Linköping University, Linköping, Sweden.
  • Hellberg S; Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden. sandra.hellberg@liu.se.
  • Papapavlou Lingehed G; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Svenvik M; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Mellergård J; Department of Obstetrics and Gynecology, Region Kalmar County, Kalmar, Sweden.
  • Dahle C; Department of Neurology, Linköping University, Linköping, Sweden.
  • Vrethem M; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Raffetseder J; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Khademi M; Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.
  • Olsson T; Department of Neurology, Linköping University, Linköping, Sweden.
  • Blomberg M; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Jenmalm MC; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Altafini C; Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Gustafsson M; Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Ernerudh J; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
J Neuroinflammation ; 20(1): 98, 2023 Apr 27.
Article en En | MEDLINE | ID: mdl-37106402
ABSTRACT

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+ and CD8+ T cells are implicated in MS pathogenesis as being key regulators of inflammation and brain lesion formation. Although Tcells are prime candidates for the pregnancy-associated improvement of MS, the precise mechanisms are yet unclear, and in particular, a deep characterization of the epigenetic and transcriptomic events that occur in peripheral T cells during pregnancy in MS is lacking.

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+ and CD8+ T cells samples. Differential analysis and network-based approaches were used to analyze the global dynamics of epigenetic and transcriptomic changes.

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:

This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4+ and CD8+ T cells during pregnancy in MS. Our findings indicate that pregnancy induces profound changes in peripheral T cells, in both MS and healthy controls, which are associated with the modulation of inflammation and MS activity.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Límite: Female / Humans / Pregnancy Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Límite: Female / Humans / Pregnancy Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia