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Prominent epigeneti...
Prominent epigenetic and transcriptomic changes in CD4(+) and CD8(+) T cells during and after pregnancy in women with multiple sclerosis and controls
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- Zenere, Alberto (author)
- Linköpings universitet,Reglerteknik,Tekniska fakulteten
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- Hellberg, Sandra (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Papapavlou Lingehed, Georgia (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
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- Svenvik, Maria (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Dept Obstet & Gynecol, Sweden
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- Mellergård, Johan (author)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Neurologiska kliniken i Linköping
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- Dahle, Charlotte (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
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- Vrethem, Magnus (author)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Neurologiska kliniken i Linköping
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- Raffetseder, Johanna (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
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- Khademi, Mohsen (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Olsson, Tomas (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Blomberg, Marie (author)
- Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, Kvinnokliniken US
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- Jenmalm, Maria (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
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- Altafini, Claudio (author)
- Linköpings universitet,Reglerteknik,Tekniska fakulteten
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- Gustafsson, Mika (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Ernerudh, Jan (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
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(creator_code:org_t)
- BMC, 2023
- 2023
- English.
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In: Journal of Neuroinflammation. - : BMC. - 1742-2094. ; 20:1
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https://urn.kb.se/re...
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Abstract
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- BackgroundMultiple 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.MethodsWomen 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.ResultsBoth 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.ConclusionThis 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Multiple sclerosis; Pregnancy; CD4(+); CD8(+); T cells; Methylation; Transcriptomics; Networks; Modules
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zenere, Alberto
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Hellberg, Sandra
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Papapavlou Linge ...
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Svenvik, Maria
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Mellergård, Joha ...
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Dahle, Charlotte
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show more...
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Vrethem, Magnus
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Raffetseder, Joh ...
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Khademi, Mohsen
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Olsson, Tomas
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Blomberg, Marie
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Jenmalm, Maria
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Altafini, Claudi ...
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Gustafsson, Mika
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Ernerudh, Jan
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show less...
- About the subject
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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 Immunology in th ...
- Articles in the publication
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Journal of Neuro ...
- By the university
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Linköping University
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Karolinska Institutet