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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.
SEEK ID: https://goeseek.gwdguser.de/studies/298
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Projects: TRR 274: Checkpoints of Central Nervous System Recovery
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Created: 3rd Aug 2026 at 12:15
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Projects: TRR 274: Checkpoints of Central Nervous System Recovery
Institutions: Universitätsmedizin Göttingen
Projects: CRC1002: Modulatory Units in Heart Failure, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells
Web page: Not specified
https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...
Programme: Sonderforschungsbereiche/Collaborative Research Centers
Public web page: https://www.sfb274.de/
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: 1 hidden item
Organisms: Mouse
SOPs: No SOPs
Data files: Innate immune memory after brain injury drives ..., Innate immune memory after brain injury drives ..., Innate immune memory after brain injury drives ..., Innate immune memory after brain injury drives ...
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Epigenomics
Technology type: Technology Type
Investigation: 1 hidden item
Organisms: Mouse
SOPs: No SOPs
Data files: Innate immune memory after brain injury drives ...
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Epigenomics
Technology type: Sequencing
Investigation: 1 hidden item
Organisms: Mouse
SOPs: No SOPs
Data files: Innate immune memory after brain injury drives ...
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: 1 hidden item
Organisms: Human
SOPs: No SOPs
Data files: Innate immune memory after brain injury drives ...
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Epigenomics
Technology type: Sequencing
Investigation: 1 hidden item
Organisms: Mouse
SOPs: No SOPs
Data files: Innate immune memory after brain injury drives ...
Snapshots: No snapshots
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: Camilla Giudici
Investigations: 1 hidden item
Bulk mRNA sequencing of human heart paraffin embeded samples from stroke patients and control patients
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
Bulk ATAC sequencing of mouse HSPC-enriched BM cells treated with recombinant IL-1b or vehicle
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
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: Camilla Giudici
Investigations: 1 hidden item
A single-cell RNA experiment was performed on cardiac interstitial cells from mice one month after stroke or control conditions
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
A single-cell RNA experiment was performed on bone marrow myeloid progenitor and mature cells chronically after stroke
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
A single-cell RNA experiment was performed on blood and heart myeloid cells from BM-depleted recipient mice that were transplanted with bone marrow cells from stroke or control donors.
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
Three independent mouse single-cell RNA experiments were performed on myeloid cells from different peripheral organs (blood, spleen, heart, lung, liver) and bone marrow, chronically after stroke and control conditions.
Creators: None
Submitter: Camilla Giudici
Investigations: 1 hidden item
Abstract
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, Ozgun Gokce, Martin Dichgans, Peter U. Heuschmann, Kinta Hatakeyama, Eduardo Beltrán, Sebastian Clauss, Boyan Bonev, Christian Schulz, Arthur Liesz
Date Published: 1st Aug 2024
Publication Type: Journal Article
DOI: 10.1016/j.cell.2024.06.028
Citation: Cell 187(17):4637-4655.e26.
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https://orcid.org/0000-0002-9069-2594