Innate immune memory after brain injury drives inflammatory cardiac dysfunction.
Cell
; 187(17): 4637-4655.e26, 2024 Aug 22.
Article
de 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lésions encéphaliques
/
Monocytes
/
Interleukine-1 bêta
/
Immunité innée
/
Mémoire immunologique
/
Inflammation
/
Souris de lignée C57BL
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Cell
Année:
2024
Type de document:
Article
Pays d'affiliation:
Espagne
Pays de publication:
États-Unis d'Amérique