Researchers have reduced scar formation and improved heart function in mice with heart failure using a monoclonal antibody. In a recent study published in Nature , researchers investigated the immune-fibroblast communication in human cardiac disease and mouse models. They found that interleukin 1 beta (IL-1β) signaling between C-C chemokine receptor type 2 (CCR2+) macrophages and fibroblasts contributes to cardiac fibrosis and disrupting IL-1β signaling potentially reduces fibrosis and improves heart function.
Background Inflammation and fibrosis, key factors in heart dysfunction, are prevalent in various heart diseases, particularly myocardial infarction (MI) and cardiomyopathies. Despite its clinical significance, there remains a dearth of therapeutic strategies targeting fibrosis. While mouse models have been used to identify the subtypes of fibroblasts involved in cardiac injury, the exact fibroblast populations driving fibrosis in human hearts, along with their regulatory mechanisms, remain unclear.
Preclinical models do not fully capture human fibroblast subtypes. High-throughput sequencing technologies, such as single-nucleus ribonucleic acid sequencing (snRNA-seq), have advanced our understanding of heart disease, but these studies lack detailed cellular transcriptomic, epigenetic, and proteomic data. Additionally, challenges in obtaining fresh human cardiac tissue have prevented large-scale studies using single-cell or epitope-based sequencing to uncover immune-fib.