TY  - JOUR
AU  - Simats, Alba
AU  - Zhang, Sijia
AU  - Messerer, Denise
AU  - Chong, Faye
AU  - Beşkardeş, Sude
AU  - Chivukula, Aparna Sharma
AU  - Cao, Jiayu
AU  - Besson-Girard, Simon
AU  - Montellano, Felipe A
AU  - Morbach, Caroline
AU  - Carofiglio, Olga
AU  - Ricci, Alessio
AU  - Roth, Stefan
AU  - Llovera, Gemma
AU  - Singh, Rashween
AU  - Chen, Yiming
AU  - Filser, Severin
AU  - Plesnila, Nikolaus
AU  - Braun, Christian
AU  - Spitzer, Hannah
AU  - Gokce, Ozgun
AU  - Dichgans, Martin
AU  - Heuschmann, Peter U
AU  - Hatakeyama, Kinta
AU  - Beltrán, Eduardo
AU  - Clauss, Sebastian
AU  - Bonev, Boyan
AU  - Schulz, Christian
AU  - Liesz, Arthur
TI  - Innate immune memory after brain injury drives inflammatory cardiac dysfunction.
JO  - Cell
VL  - 187
IS  - 17
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2024-01059
SP  - 4637 - 4655.e26
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Immunity, Innate
KW  - Mice
KW  - Interleukin-1beta: metabolism
KW  - Brain Injuries: immunology
KW  - Humans
KW  - Male
KW  - Monocytes: metabolism
KW  - Monocytes: immunology
KW  - Immunologic Memory
KW  - Mice, Inbred C57BL
KW  - Inflammation: immunology
KW  - Macrophages: immunology
KW  - Macrophages: metabolism
KW  - Stroke: complications
KW  - Stroke: immunology
KW  - Heart Diseases: immunology
KW  - Female
KW  - Receptors, CCR2: metabolism
KW  - Fibrosis
KW  - Epigenesis, Genetic
KW  - Trained Immunity
KW  - brain ischemia (Other)
KW  - cardiac fibrosis (Other)
KW  - cenicriviroc (Other)
KW  - innate immune memory (Other)
KW  - interleukin-1 (Other)
KW  - myeloid cells (Other)
KW  - stroke (Other)
KW  - systemic inflammation (Other)
KW  - trained immunity (Other)
KW  - Interleukin-1beta (NLM Chemicals)
KW  - Receptors, CCR2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39043180
DO  - DOI:10.1016/j.cell.2024.06.028
UR  - https://pub.dzne.de/record/271707
ER  -