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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 187, Heft: 17, Seiten: 4637-4655.e26 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Pioneer Campus (HPC)
Förderungen 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