Journal Article

DZNE-2024-01059

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Innate immune memory after brain injury drives inflammatory cardiac dysfunction.

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.Extern* ; Chen, Y. ; Filser, S.Extern* ; Plesnila, N. ; Braun, C. ; Spitzer, H. ; Gokce, O.DZNE* ; Dichgans, M.DZNE* ; Heuschmann, P. U. ; Hatakeyama, K. ; Beltrán, E. ; Clauss, S. ; Bonev, B. ; Schulz, C. ; Liesz, A.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2024.06.028

Abstract: 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.

Keyword(s): Animals (MeSH) ; Immunity, Innate (MeSH) ; Mice (MeSH) ; Interleukin-1beta: metabolism (MeSH) ; Brain Injuries: immunology (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Monocytes: metabolism (MeSH) ; Monocytes: immunology (MeSH) ; Immunologic Memory (MeSH) ; Mice, Inbred C57BL (MeSH) ; Inflammation: immunology (MeSH) ; Macrophages: immunology (MeSH) ; Macrophages: metabolism (MeSH) ; Stroke: complications (MeSH) ; Stroke: immunology (MeSH) ; Heart Diseases: immunology (MeSH) ; Female (MeSH) ; Receptors, CCR2: metabolism (MeSH) ; Fibrosis (MeSH) ; Epigenesis, Genetic (MeSH) ; Trained Immunity (MeSH) ; brain ischemia ; cardiac fibrosis ; cenicriviroc ; innate immune memory ; interleukin-1 ; myeloid cells ; stroke ; systemic inflammation ; trained immunity ; Interleukin-1beta ; Receptors, CCR2

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
2. Spatial Dynamics of Neurodegeneration (AG Gokce)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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