Role of CD4+ T-cells for the regulation of myelopoiesis in response to myocardial infarction

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Monocyte derived cells are central players during healing and remodelling after myocardial infarction. Myocardial infarction triggers monocyte production (myelopoiesis) both in the spleen and in the bone marrow. High myelopoietic activity as indicated by high monocyte blood counts is associated with a worse clinical prognosis after myocardial infarction. Obesity constitutes an important comorbidity in myocardial infarction patients and is described to promote myelopoiesis. Thereby, it likely enhances atherosclerosis and might also impair myocardial healing and remodelling processes.Our own experimental data further indicate that CD4+ T-cells modulate both the differentiation of monocyte derived cells in the myocardium and myelopoiesis in the spleen after a myocardial infarction. Based on this, we aim to study the following scientific questions in the proposed research project: Does myelopoiesis and monocyte differentiation differ in the spleen and in the bone marrow in the course after an experimental myocardial infarction? What is the impact of obesity on these processes? How do CD4+ T-cells regulate the myelopoiesis and the monocyte differentiation in these organs? Is the stimulation of regulatory T-cells a therapeutic approach that has a beneficial effect on both myelopoiesis and outcome parameters after an experimental myocardial infaction? This research program will evaluate clinical translatable therapeutic approaches and includes analyses of human specimen and data.