Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic macrophage programming during CVB3-induced viral myocarditis
Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the innate immunity. Whether stabilin-1 affects the inflammatory response during viral myocarditis (VM) is entirely u...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 2022
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| In: |
Journal of molecular and cellular cardiology
Year: 2022, Volume: 165, Pages: 31-39 |
| ISSN: | 1095-8584 |
| DOI: | 10.1016/j.yjmcc.2021.12.009 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.yjmcc.2021.12.009 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0022282821002364 
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| Author Notes: | Paolo Carai, Anna Pia Papageorgiou, Sophie Van Linthout, Sophie Deckx, Sebastiaan Velthuis, Esther Lutgens, Erwin Wijnands, Carsten Tschöpe, Christina Schmuttermaier, Julia Kzhyshkowska, Elizabeth Anne Vincent Jones, Stephane Heymans |
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| 245 | 1 | 0 | |a Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic macrophage programming during CVB3-induced viral myocarditis |c Paolo Carai, Anna Pia Papageorgiou, Sophie Van Linthout, Sophie Deckx, Sebastiaan Velthuis, Esther Lutgens, Erwin Wijnands, Carsten Tschöpe, Christina Schmuttermaier, Julia Kzhyshkowska, Elizabeth Anne Vincent Jones, Stephane Heymans |
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| 520 | |a Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the innate immunity. Whether stabilin-1 affects the inflammatory response during viral myocarditis (VM) is entirely unknown. Here, we assess the role of stabilin-1 in the pathogenesis of VM and its suitability as a therapeutic target. Genetic loss of stabilin-1 increased mortality and cardiac necrosis in a mouse model of human Coxsackievirus B3 (CVB3)-induced myocarditis. Absence of stabilin-1 significantly reduced monocyte recruitment and strongly reduced the number of alternatively activated anti-inflammatory macrophages in the heart, enhancing a pro-inflammatory cardiac niche with a detrimental T lymphocyte response during VM. Yeast two-hybrid screening, confirmed by affinity chromatography, identified fibronectin as a stabilin-1 interacting partner. Absence of stabilin-1 specifically decreased monocyte adhesion on extracellular fibronectin in vitro. Loss of Type III repeats Extra Domain A (EDA) of fibronectin during VM also increased the mortality and cardiac necrosis as in stabilin-1 knockout mice, with reduced monocytic cardiac recruitment and increased T lymphocyte response. Collectively, stabilin-1 has an immune-suppressive role of limiting myocardial damage during VM, regulating anti-inflammatory monocyte-recruitment to the site of inflammation. | ||
| 650 | 4 | |a Fibronectin | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Monocytes | |
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| 650 | 4 | |a Viral myocarditis | |
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| 700 | 1 | |a Van Linthout, Sophie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Deckx, Sophie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Velthuis, Sebastiaan |e VerfasserIn |4 aut | |
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