Fibroblast and Immune Cell Cross-Talk in Cardiac Fibrosis.

Abstract

The intricate interplay between inflammatory and reparative responses in the context of heart injury is central to the pathogenesis of heart failure. Recent clinical studies have shown the therapeutic benefits of anti-inflammatory strategies in the treatment of cardiovascular diseases. This review provides a comprehensive overview of the cross-talk between immune cells and fibroblasts in the diseased heart. The role of inflammatory cells in fibroblast activation after cardiac injury is well-documented, but recent single-cell transcriptomics studies have identified putative pro-inflammatory fibroblasts in the infarcted heart, suggesting that fibroblasts, in turn, can modify inflammatory cell behavior. Furthermore, anti-inflammatory immune cells and fibroblasts have been described. The use of spatial and temporal-omics analyses may provide additional insights toward a better understanding of disease-specific microenvironments, where activated fibroblasts and inflammatory cells are in proximity. Recent studies focused on the interplay between fibroblasts and immune cells have brought us closer to the identification of cell type-specific targets for intervention. Further exploration of these intercellular communications will provide deeper insights toward the development of novel therapeutics.