| First Author | Simats A | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 17 | Pages | 4637-4655.e26 |
| PubMed ID | 39043180 | Mgi Jnum | J:353453 |
| Mgi Id | MGI:7710783 | Doi | 10.1016/j.cell.2024.06.028 |
| Citation | Simats A, et al. (2024) Innate immune memory after brain injury drives inflammatory cardiac dysfunction. Cell |
| abstractText | 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-1beta 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-1beta 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-1beta-mediated comorbidities, offering a framework for secondary prevention immunotherapy. |
