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000271707 1001_ $$aSimats, Alba$$b0
000271707 245__ $$aInnate immune memory after brain injury drives inflammatory cardiac dysfunction.
000271707 260__ $$aNew York, NY$$bElsevier$$c2024
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000271707 520__ $$aThe medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1β was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
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000271707 650_7 $$2Other$$abrain ischemia
000271707 650_7 $$2Other$$acardiac fibrosis
000271707 650_7 $$2Other$$acenicriviroc
000271707 650_7 $$2Other$$ainnate immune memory
000271707 650_7 $$2Other$$ainterleukin-1
000271707 650_7 $$2Other$$amyeloid cells
000271707 650_7 $$2Other$$astroke
000271707 650_7 $$2Other$$asystemic inflammation
000271707 650_7 $$2Other$$atrained immunity
000271707 650_7 $$2NLM Chemicals$$aInterleukin-1beta
000271707 650_7 $$2NLM Chemicals$$aReceptors, CCR2
000271707 650_2 $$2MeSH$$aAnimals
000271707 650_2 $$2MeSH$$aImmunity, Innate
000271707 650_2 $$2MeSH$$aMice
000271707 650_2 $$2MeSH$$aInterleukin-1beta: metabolism
000271707 650_2 $$2MeSH$$aBrain Injuries: immunology
000271707 650_2 $$2MeSH$$aHumans
000271707 650_2 $$2MeSH$$aMale
000271707 650_2 $$2MeSH$$aMonocytes: metabolism
000271707 650_2 $$2MeSH$$aMonocytes: immunology
000271707 650_2 $$2MeSH$$aImmunologic Memory
000271707 650_2 $$2MeSH$$aMice, Inbred C57BL
000271707 650_2 $$2MeSH$$aInflammation: immunology
000271707 650_2 $$2MeSH$$aMacrophages: immunology
000271707 650_2 $$2MeSH$$aMacrophages: metabolism
000271707 650_2 $$2MeSH$$aStroke: complications
000271707 650_2 $$2MeSH$$aStroke: immunology
000271707 650_2 $$2MeSH$$aHeart Diseases: immunology
000271707 650_2 $$2MeSH$$aFemale
000271707 650_2 $$2MeSH$$aReceptors, CCR2: metabolism
000271707 650_2 $$2MeSH$$aFibrosis
000271707 650_2 $$2MeSH$$aEpigenesis, Genetic
000271707 650_2 $$2MeSH$$aTrained Immunity
000271707 7001_ $$aZhang, Sijia$$b1
000271707 7001_ $$aMesserer, Denise$$b2
000271707 7001_ $$aChong, Faye$$b3
000271707 7001_ $$aBeşkardeş, Sude$$b4
000271707 7001_ $$aChivukula, Aparna Sharma$$b5
000271707 7001_ $$aCao, Jiayu$$b6
000271707 7001_ $$aBesson-Girard, Simon$$b7
000271707 7001_ $$aMontellano, Felipe A$$b8
000271707 7001_ $$aMorbach, Caroline$$b9
000271707 7001_ $$aCarofiglio, Olga$$b10
000271707 7001_ $$aRicci, Alessio$$b11
000271707 7001_ $$aRoth, Stefan$$b12
000271707 7001_ $$aLlovera, Gemma$$b13
000271707 7001_ $$0P:(DE-2719)9001810$$aSingh, Rashween$$b14$$udzne
000271707 7001_ $$aChen, Yiming$$b15
000271707 7001_ $$0P:(DE-2719)2810523$$aFilser, Severin$$b16$$udzne
000271707 7001_ $$0P:(DE-2719)9000853$$aPlesnila, Nikolaus$$b17
000271707 7001_ $$aBraun, Christian$$b18
000271707 7001_ $$aSpitzer, Hannah$$b19
000271707 7001_ $$0P:(DE-2719)9002754$$aGokce, Ozgun$$b20$$udzne
000271707 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b21$$udzne
000271707 7001_ $$aHeuschmann, Peter U$$b22
000271707 7001_ $$aHatakeyama, Kinta$$b23
000271707 7001_ $$aBeltrán, Eduardo$$b24
000271707 7001_ $$aClauss, Sebastian$$b25
000271707 7001_ $$aBonev, Boyan$$b26
000271707 7001_ $$aSchulz, Christian$$b27
000271707 7001_ $$aLiesz, Arthur$$b28
000271707 773__ $$0PERI:(DE-600)2001951-8$$a10.1016/j.cell.2024.06.028$$gVol. 187, no. 17, p. 4637 - 4655.e26$$n17$$p4637 - 4655.e26$$tCell$$v187$$x0092-8674$$y2024
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