Cells of the innate immune system play an important role in organs and tissues of the body. They regulate organ functions and homeostasis, and they contribute to tissue regeneration. However, immune cells are also crucially involved in inflammatory processes that negatively influence tissue remodeling and promote infarct damage or other fibrotic changes. My research group is working extensively on the question of how the immune response of myeloid cells must be modulated in order to limit pro-inflammatory processes and positively influence tissue remodeling and regeneration. The underlying molecular and pathophysiological relationships are still poorly understood.

The function of immune cells is regulated at various molecular (e.g. transcription, post-transcriptional mechanisms) and cellular (e.g. immunoreceptors) levels. These processes are poorly understood. In particular, it is unclear what effects regulatory molecules have on the function of innate immune cells in cardiovascular tissues and what effects their modulation has on infarct size and inflammatory remodeling processes. In addition to the molecular regulation of immune cells by local and systemic signals, the developmental origin of immune cells also plays a role according to the latest findings. We and other research groups have been able to show that tissue macrophages originate to a large extent from early embryonic development and then persist in cardiovascular and other tissues and renew themselves independently of hematopoietic stem cells. These macrophages have a different genetic program from bone marrow-derived macrophages. Therefore, we perform differentiated studies using lineage tracing and fate mapping analyses, which, complemented by bioinformatic analyses, comprehensively address the molecular regulation of immune cells in cardiovascular tissues and ultimately lead to new therapeutic strategies in inflammatory diseases of the cardiovascular system.

Methods:

• Detailed immunophenotyping in humans and animals
• Functional analysis of myeloid immune cells, hematopoietic progenitor cells and platelets
• Translational disease models with a cardiovascular focus in mice: myocardial infarction, heart failure, arterial hypertension, atherosclerosis
• Temporally and spatially controlled labeling (fate mapping, lineage tracing) and depletion (lineage depletion) of myeloid immune cells
• Intravital microscopy of inflammatory processes as well as immune cell development and migration in the mouse model
• Analysis of immune metabolism