Myocardial Immune Niches in Homeostasis and Inflammation

The heart functions as a circulatory pump that supplies blood throughout the body. The execution of this critical function depends on the interplay between cardiomyocytes and the supportive cellular infrastructure, generated by endothelial cells, fibroblasts and distinct immune cell populations. Immune cells cooperate with fibroblastic and endothelial stromal cells across different cellular ecosystems to maintain tissue integrity and function. In the homeostatic state, immune-stromal interactions in specific niche environments govern critical cardiomyocyte functions such as contractility and metabolic balance. Inflammatory perturbations disrupt the equilibrated cellular interactions leading to local stromal and immune cell activation. Dedicated regulatory mechanisms and circuits direct immune cell functions in the inflamed myocardium to prevent maladaptive remodeling processes, which could manifest as cardiac fibrosis, arrhythmia, or heart failure. Here, we discuss an immune niche-based view on myocardial immunity based on anatomically and functionally distinct niche environments. We summarize recent progress on the key molecular and cellular components and their interactions within cardiac immune niches and highlight immunological mechanisms and pathways that maintain cardiomyocyte integrity and function.