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Cell-specific and d...
Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease
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- Lacy, Michael (författare)
- German Centre for Cardiovascular Research,University Hospital Munich
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- Bürger, Christina (författare)
- University Hospital Munich
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- Shami, Annelie (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups
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- Ahmadsei, Maiwand (författare)
- German Centre for Cardiovascular Research,University Hospital Munich
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- Winkels, Holger (författare)
- University Hospital Munich,University Hospital of Cologne
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- Nitz, Katrin (författare)
- German Centre for Cardiovascular Research,University Hospital Munich
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- van Tiel, Claudia M. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Seijkens, Tom T.P. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Kusters, Pascal J.H. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Karshovka, Ela (författare)
- University Hospital Munich
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- Prange, Koen H.M. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Wu, Yuting (författare)
- University Hospital Munich
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- Brouns, Sanne L.N. (författare)
- Maastricht University Medical Centre
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- Unterlugauer, Sigrid (författare)
- University Hospital Munich
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- Kuijpers, Marijke J.E. (författare)
- Maastricht University Medical Centre
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- Reiche, Myrthe E. (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Steffens, Sabine (författare)
- University Hospital Munich,German Centre for Cardiovascular Research
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- Edsfeldt, Andreas (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital
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- Megens, Remco T.A. (författare)
- University Hospital Munich
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- Heemskerk, Johan W.M. (författare)
- Maastricht University Medical Centre
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- Goncalves, Isabel (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital
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- Weber, Christian (författare)
- German Centre for Cardiovascular Research,Munich Cluster for Systems Neurology,University Hospital Munich,Maastricht University Medical Centre
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- Gerdes, Norbert (författare)
- University Hospital of Düsseldorf,University Hospital Munich
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- Atzler, Dorothee (författare)
- Ludwig-Maximilian University of Munich,University Hospital Munich,German Centre for Cardiovascular Research
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- Lutgens, Esther (författare)
- German Centre for Cardiovascular Research,University Hospital Munich,Academic Medical Center of University of Amsterdam (AMC)
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(creator_code:org_t)
- 2021-06-18
- 2021
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.
Ämnesord
- 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)
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Lacy, Michael
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Bürger, Christin ...
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Shami, Annelie
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Ahmadsei, Maiwan ...
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Winkels, Holger
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Nitz, Katrin
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van Tiel, Claudi ...
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Seijkens, Tom T. ...
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Kusters, Pascal ...
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Karshovka, Ela
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Prange, Koen H.M ...
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Wu, Yuting
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Brouns, Sanne L. ...
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Unterlugauer, Si ...
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Kuijpers, Marijk ...
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Reiche, Myrthe E ...
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Steffens, Sabine
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Edsfeldt, Andrea ...
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Megens, Remco T. ...
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Heemskerk, Johan ...
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Goncalves, Isabe ...
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Weber, Christian
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Gerdes, Norbert
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Atzler, Dorothee
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Lutgens, Esther
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