Innate immune memory after brain injury drives inflammatory cardiac dysfunction.
Cell
; 187(17): 4637-4655.e26, 2024 Aug 22.
Article
en En
| MEDLINE
| ID: mdl-39043180
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-1ß 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-1ß 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-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
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Monocitos
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Interleucina-1beta
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Inmunidad Innata
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Memoria Inmunológica
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Inflamación
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Ratones Endogámicos C57BL
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Año:
2024
Tipo del documento:
Article