Spatially clustered type I interferon responses at injury borderzones.

ABSTRACT: Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone^1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmac

SUBMITTER: Ninh VK 

PROVIDER: S-EPMC11374671 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature