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@ARTICLE{Simats:271707,
author = {Simats, Alba and Zhang, Sijia and Messerer, Denise and
Chong, Faye and Beşkardeş, Sude and Chivukula, Aparna
Sharma and Cao, Jiayu and Besson-Girard, Simon and
Montellano, Felipe A and Morbach, Caroline and Carofiglio,
Olga and Ricci, Alessio and Roth, Stefan and Llovera, Gemma
and Singh, Rashween and Chen, Yiming and Filser, Severin and
Plesnila, Nikolaus and Braun, Christian and Spitzer, Hannah
and Gokce, Ozgun and Dichgans, Martin and Heuschmann, Peter
U and Hatakeyama, Kinta and Beltrán, Eduardo and Clauss,
Sebastian and Bonev, Boyan and Schulz, Christian and Liesz,
Arthur},
title = {{I}nnate immune memory after brain injury drives
inflammatory cardiac dysfunction.},
journal = {Cell},
volume = {187},
number = {17},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2024-01059},
pages = {4637 - 4655.e26},
year = {2024},
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.},
keywords = {Animals / Immunity, Innate / Mice / Interleukin-1beta:
metabolism / Brain Injuries: immunology / Humans / Male /
Monocytes: metabolism / Monocytes: immunology / Immunologic
Memory / Mice, Inbred C57BL / Inflammation: immunology /
Macrophages: immunology / Macrophages: metabolism / Stroke:
complications / Stroke: immunology / Heart Diseases:
immunology / Female / Receptors, CCR2: metabolism / Fibrosis
/ Epigenesis, Genetic / Trained Immunity / brain ischemia
(Other) / cardiac fibrosis (Other) / cenicriviroc (Other) /
innate immune memory (Other) / interleukin-1 (Other) /
myeloid cells (Other) / stroke (Other) / systemic
inflammation (Other) / trained immunity (Other) /
Interleukin-1beta (NLM Chemicals) / Receptors, CCR2 (NLM
Chemicals)},
cin = {AG Dichgans / AG Gokce},
ddc = {610},
cid = {I:(DE-2719)5000022 / I:(DE-2719)1013041},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39043180},
doi = {10.1016/j.cell.2024.06.028},
url = {https://pub.dzne.de/record/271707},
}