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

单核细胞衍生的细胞是心肌梗死后愈合和重塑过程中的核心参与者。心肌梗死触发脾和骨髓中单核细胞的产生（骨髓生成）。高单核细胞血细胞计数表明高骨髓生成活性与心肌梗死后较差的临床预后相关。肥胖是心肌梗死患者的一种重要合并症，并被描述为促进骨髓生成。因此，它可能会增强动脉粥样硬化，也可能会损害心肌愈合和重塑processes.Our自己的实验数据进一步表明，CD 4 + T-细胞调节单核细胞衍生的细胞在心肌和骨髓细胞在脾分化心肌梗死后。在此基础上，我们的目的是研究以下科学问题在拟议的研究项目：骨髓和单核细胞分化不同的脾脏和骨髓在实验性心肌梗死后的过程中？肥胖对这些过程有什么影响？CD 4 + T细胞如何调节这些器官中的骨髓生成和单核细胞分化？在实验性心肌梗死后，刺激调节性T细胞是否是一种对骨髓生成和预后参数都有有益影响的治疗方法？这项研究计划将评估临床可翻译的治疗方法，包括对人体标本和数据的分析。

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.