Cardiac Immunology: A New Era for Immune Cells in the Heart.

The immune system is essential for the development and homeostasis of the human body. Our current understanding of the immune system on disease pathogenesis has drastically expanded over the last decade with the definition of additional non-canonical roles in various tissues. Recently, tissue-resident immune cells have become an important research topic for understanding their roles in the prevention, pathogenesis, and recovery from the diseases. Heart resident immune cells, particularly macrophage subtypes, and their characteristic morphology, distribution in the cardiac tissue, and transcriptional profile have been recently reported in the experimental animal models, unrevealing novel and unexpected roles in electrophysiological regulation of the heart both at the steady-state and diseased state. Immunological processes have been widely studied in both sterile cardiac disorders, such as myocardial infarction, autoimmune cardiac diseases, or infectious cardiac diseases, such as myocarditis, endocarditis, and acute rheumatic carditis. Following cardiac injury, innate and adaptive immunity have critical roles in pro- and anti-inflammatory processes. Heart resident immune cells not only provide defense against infectious diseases but also contribute to the homeostasis. In recent years, physiological changes and pathological processes were demonstrated to alter the abundance, distribution, polarization, and diversity of immune cells in the heart. Accumulating evidence indicates that cardiac remodeling is controlled by the complex crosstalk between cardiomyocytes and cardiac immune cells through the gap junctions, providing the ion flow to achieve synchronization and modulation of contractility. This review article aims to review the well-documented roles of both resident and recruited immune cell in the heart, as well as their recently uncovered unconventional roles in both cardiac homeostasis and cardiovascular diseases. We have mostly focused on studies on animal models used in preclinical research, underlying the need for further investigations in humans or in vitro human models. It may be foreseen that the further comprehensive investigations of cardiac immunology might harbor new therapeutic options for cardiac disorders that have tremendous medical potential.