Innate immune memory after brain injury drives inflammatory cardiac dysfunction
Actions 
Order Assays
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.
Export PNG
Download
Creators and Submitter
Views: 80
Created: 5th Jul 2024 at 09:43
Last updated: 14th Oct 2024 at 12:10
TagsThis item has not yet been tagged.
Related items
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets
Institutions: LMU
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Research Data Steward
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).
To explore investigations and their associated studies in more detail, please visit the 'Related items' tab on the Project ...
Public web page: Not specified
Submitter: Rainer Malik
Studies: A genome-wide in vivo CRISPR screen identifies essential regulators of T..., Adult neural stem cell activation in mice is regulated by the day/night ..., Diet triggers specific responses of hypothalamic astrocytes in time and ..., Direct neuronal reprogramming of NDUFS4 patient cells identifies the unf..., Distinct molecular profiles of skull bone marrow in health and neurologi..., Early adaptive immune activation detected in monozygotic twins with prod..., Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the..., High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-..., Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque V..., Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitme..., Innate immune memory after brain injury drives inflammatory cardiac dysf..., MicroRNAs from extracellular vesicles as a signature for Parkinson's dis..., Microglia in white matter aging, Molecular diversity of diencephalic astrocytes reveals adult astrogenesi..., Multiomic ALS signatures highlight subclusters and sex differences sugge..., Multi‐omic landscaping of human midbrains identifies disease‐relevant mo..., Myelin degeneration in leucodystrophies, Oligodendrocytes in AD models, Oligodendrocytes in white matter aging, Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astro..., Peripheral expression of brain-penetrant progranulin rescues pathologies..., Phagocyte-mediated synapse removal in cortical neuroinflammation is prom..., Shared inflammatory glial cell signature after stab wound injury, reveal..., Skin and gut imprinted helper T cell subsets exhibit distinct functional..., Spatial Transcriptomics-correlated Electron Microscopy maps transcriptio..., Spatial centrosome proteome of human neural cells uncovers disease-relev..., T cells modulate the microglial response to brain ischemia, Twin study identifies early immunological and metabolic dysregulation of...
Assays: Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human) + smallRNA-seq (human), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (rat), Expression profiling: MERFISH Spatial Transcriptomics (mouse), Expression profiling: Microarray (zebrafish), Expression profiling: RiboTag-mRNA-seq (mouse), Expression profiling: Small RNA-seq (human), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics correlated Electron Micros..., Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human) (Day 20), Expression profiling: scRNA-seq (human) (Day 5), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse) + Bulk RNA-seq (mouse), Expression profiling: small RNA-seq (human), Expression profiling: small RNA-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: CUT&Tag sequencing (mouse), Genome binding/occupancy profiling: snATAC-seq (mouse), Genome wide (GW) and validation CRISPR screens (rat)
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Epigenomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Epigenomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Epigenomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
CUT&tag sequencing of mouse BM monocytes and HSPC-enriched myeloid cells from mice one month after stroke or control conditions was performed
Creators: None
Submitter: Aditi Methi
External LinkBulk mRNA sequencing of human heart paraffin embeded samples from stroke patients and control patients
Creators: None
Submitter: Aditi Methi
Bulk ATAC sequencing of mouse HSPC-enriched BM cells treated with recombinant IL-1b or vehicle
Creators: None
Submitter: Aditi Methi
Mouse single-nuclei ATAC experiment performed on myeloid cells from bone marrow chronically after stroke and control conditions. An additional group of bone marrow cells from stroke mice treated with neutralizing antibodies against IL-1b was also included (stroke-treated group).
Creators: None
Submitter: Aditi Methi
A single-cell RNA experiment was performed on cardiac interstitial cells from mice one month after stroke or control conditions
Creators: None
Submitter: Aditi Methi
Abstract (Expand)
Authors: Alba Simats, Sijia Zhang, Denise Messerer, Faye Chong, Sude Beşkardeş, Aparna Sharma Chivukula, Jiayu Cao, Simon Besson-Girard, Felipe A Montellano, Caroline Morbach, Olga Carofiglio, Alessio Ricci, Stefan Roth, Gemma Llovera, Rashween Singh, Yiming Chen, Severin Filser, Nikolaus Plesnila, Christian Braun, Hannah Spitzer, Özgün Gökçe, Martin Dichgans, Peter U Heuschmann, Kinta Hatakeyama, Eduardo Beltrán, Sebastian Clauss, Boyan Bonev, Christian Schulz, Arthur Liesz
Date Published: 22nd Jul 2024
Publication Type: Journal
