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

单核细胞来源的细胞是心肌梗死后修复和重塑的中心角色。心肌梗死会在脾和骨髓中触发单核细胞的产生(骨髓生成)。单核细胞血细胞计数高表明的高骨髓生成活性与心肌梗死后较差的临床预后有关。肥胖是心肌梗死患者的一种重要的合并症，被描述为促进骨髓生成。因此，它可能会加剧动脉粥样硬化，也可能损害心肌的愈合和重塑过程。我们自己的实验数据进一步表明，CD4+T细胞在心肌梗死后调节心肌中单核细胞来源的细胞的分化和脾中的骨髓生成。基于此，我们的目标是在拟议的研究项目中研究以下科学问题：在实验性心肌梗死后的过程中，脾和骨髓中的骨髓造血和单核细胞分化是否有所不同？肥胖对这些过程有什么影响？在这些器官中，CD4+T细胞是如何调节骨髓生成和单核细胞分化的？在实验性心肌梗死后，刺激调节性T细胞是一种对骨髓生成和预后参数都有有益影响的治疗方法吗？这项研究计划将评估临床可翻译的治疗方法，并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.