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Simats, A.* ; Zhang, S.* ; Messerer, D.* ; Chong, F. ; Beşkardeş, S. ; Chivukula, A.S.* ; Cao, J.* ; Besson-Girard, S.* ; Montellano, F.A.* ; Morbach, C.* ; Carofiglio, O.* ; Ricci, A.* ; Roth, S.* ; Llovera, G.* ; Singh, R.* ; Chen, Y.* ; Filser, S.* ; Plesnila, N.* ; Braun, C.* ; Spitzer, H.* ; Gokce, O.* ; Dichgans, M.* ; Heuschmann, P.U.* ; Hatakeyama, K.* ; Beltrán, E.* ; Clauss, S.* ; Bonev, B. ; Schulz, C.* ; Liesz, A.*

Innate immune memory after brain injury drives inflammatory cardiac dysfunction.

Cell 187, 4637-4655.e26 (2024)
Publ. Version/Full Text DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Brain Ischemia ; Cardiac Fibrosis ; Cenicriviroc ; Innate Immune Memory ; Interleukin-1 ; Myeloid Cells ; Stroke ; Systemic Inflammation ; Trained Immunity; Heart-failure; Diastolic Dysfunction; Transcription-factor; Web Server; Stroke; Macrophages; State; Arrhythmias; Predictors; Activation
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 187, Issue: 17, Pages: 4637-4655.e26 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Pioneer Campus
PSP Element(s) G-510004-001
Grants German Ministry of Research and Education
European Research Council
German Research Foundation (DFG)
Corona Foundation
China Scholarship Council
Walter-Benjamin Fellowship
Munich School for Data Science (MUDS)
UNION-CVD Clinician Scientist Programme
Vascular Dementia Research Foundation
DOI 10.1016/j.cell.2024.06.028
WOS ID 001301175700001
PubMed ID 39043180
Erfassungsdatum 2024-07-25
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