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Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
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- Hasib, Lekbira (författare)
- Linköpings universitet,Medicinska fakulteten,Avdelningen för kardiovaskulär medicin
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- Lundberg, Anna (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten
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- Zachrisson, Helene (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV,Region Östergötland, Fysiologiska kliniken US
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- Ernerudh, Jan (författare)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
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- Jonasson, Lena (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Region Östergötland, Kardiologiska kliniken US
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(creator_code:org_t)
- 2015-08-11
- 2016
- Engelska.
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Ingår i: Journal of Internal Medicine. - : WILEY-BLACKWELL. - 0954-6820 .- 1365-2796. ; 279:1, s. 63-77
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P<0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- acute coronary syndrome; coronary artery disease; immune homeostasis; inflammation; regulatory T cell
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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