Communication between cardiomyocytes and innate immune cells in failing hearts – CLARIFY

Ischemic heart Failure (IHF) is a leading cause of hospitalization and mortality in Europe. This unmet
challenge asks for a better understanding of the mechanisms causing myocardial tissue damage and the
development of new therapeutic approaches supporting cardiac repair. The immune system plays a
decisive role for initial inflammatory responses following cardiac damage and subsequent regenerative
responses. However, the interplay between immune cells and cardiomyocytes/cardiac progenitor cells
within the myocardium is not well understood. We aim to explore the spatial and temporal communication
between cardiac myocytes, cardiac stem cells and innate immune cells during IHF. We will use high-end
transcriptional profiling involving single-cell RNA-seq / tomo-seq combined with mouse genetics and large
animal models to identify new factors involved in cellular interactions responsible for cardiac remodeling.
Furthermore, we want to understand the function of crucial mediators of cardiomyocyte-innate immune cell
interactions, the Reg-family of cytokines, for post-ischemic damage control and tissue repair. Our research
will supply new approaches for the manipulation of cell-cell interactions in the failing heart. All model
organisms capable of cardiac regeneration rely on immune cells to orchestrate different waves of
inflammation, matrix deposition, angiogenesis and cardiomyocyte proliferation. Hence, therapeutic
manipulation of local immune cell-dependent processes in the damaged heart might shift the balance
between extensive scarring, minimal defect healing and regeneration.