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Innate immune memory after brain injury drives inflammatory cardiac dysfunction

The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored....

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Main Authors: Simats, Alba (Author) , Zhang, Sijia (Author) , Messerer, Denise (Author) , Chong, Faye (Author) , Beşkardeş, Sude (Author) , Chivukula, Aparna Sharma (Author) , Cao, Jiayu (Author) , Besson-Girard, Simon (Author) , Montellano, Felipe A. (Author) , Morbach, Caroline (Author) , Carofiglio, Olga (Author) , Ricci, Alessio (Author) , Roth, Stefan (Author) , Llovera, Gemma (Author) , Singh, Rashween (Author) , Chen, Yiming (Author) , Filser, Severin (Author) , Plesnila, Nikolaus (Author) , Braun, Christian (Author) , Spitzer, Hannah (Author) , Gokce, Ozgun (Author) , Dichgans, Martin (Author) , Heuschmann, Peter (Author) , Hatakeyama, Kinta (Author) , Beltrán, Eduardo (Author) , Clauss, Sebastian (Author) , Bonev, Boyan (Author) , Schulz, Christian (Author) , Liesz, Arthur (Author)
Format: Article (Journal)
Language:English
Published: 22 August 2024
In: Cell
Year: 2024, Volume: 187, Issue: 17, Pages: 4637-4655.e26
ISSN:1097-4172
DOI:10.1016/j.cell.2024.06.028
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2024.06.028
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867424007025
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Author Notes:Alba Simats, Sijia Zhang, Denise Messerer, Faye Chong, Sude Beşkardeş, Aparna Sharma Chivukula, Jiayu Cao, Simon Besson-Girard, Felipe A. Montellano, Caroline Morbach, Olga Carofiglio, Alessio Ricci, Stefan Roth, Gemma Llovera, Rashween Singh, Yiming Chen, Severin Filser, Nikolaus Plesnila, Christian Braun, Hannah Spitzer, Ozgun Gokce, Martin Dichgans, Peter U. Heuschmann, Kinta Hatakeyama, Eduardo Beltrán, Sebastian Clauss, Boyan Bonev, Christian Schulz, Arthur Liesz

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520 |a The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1β was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy. 
650 4 |a brain ischemia 
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