%0 Journal Article
%A Simats, Alba
%A Zhang, Sijia
%A Messerer, Denise
%A Chong, Faye
%A Beşkardeş, Sude
%A Chivukula, Aparna Sharma
%A Cao, Jiayu
%A Besson-Girard, Simon
%A Montellano, Felipe A
%A Morbach, Caroline
%A Carofiglio, Olga
%A Ricci, Alessio
%A Roth, Stefan
%A Llovera, Gemma
%A Singh, Rashween
%A Chen, Yiming
%A Filser, Severin
%A Plesnila, Nikolaus
%A Braun, Christian
%A Spitzer, Hannah
%A Gokce, Ozgun
%A Dichgans, Martin
%A Heuschmann, Peter U
%A Hatakeyama, Kinta
%A Beltrán, Eduardo
%A Clauss, Sebastian
%A Bonev, Boyan
%A Schulz, Christian
%A Liesz, Arthur
%T Innate immune memory after brain injury drives inflammatory cardiac dysfunction.
%J Cell
%V 187
%N 17
%@ 0092-8674
%C New York, NY
%I Elsevier
%M DZNE-2024-01059
%P 4637 - 4655.e26
%D 2024
%X 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.
%K Animals
%K Immunity, Innate
%K Mice
%K Interleukin-1beta: metabolism
%K Brain Injuries: immunology
%K Humans
%K Male
%K Monocytes: metabolism
%K Monocytes: immunology
%K Immunologic Memory
%K Mice, Inbred C57BL
%K Inflammation: immunology
%K Macrophages: immunology
%K Macrophages: metabolism
%K Stroke: complications
%K Stroke: immunology
%K Heart Diseases: immunology
%K Female
%K Receptors, CCR2: metabolism
%K Fibrosis
%K Epigenesis, Genetic
%K Trained Immunity
%K brain ischemia (Other)
%K cardiac fibrosis (Other)
%K cenicriviroc (Other)
%K innate immune memory (Other)
%K interleukin-1 (Other)
%K myeloid cells (Other)
%K stroke (Other)
%K systemic inflammation (Other)
%K trained immunity (Other)
%K Interleukin-1beta (NLM Chemicals)
%K Receptors, CCR2 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39043180
%R 10.1016/j.cell.2024.06.028
%U https://pub.dzne.de/record/271707