Department of Internal Medicine I, University Clinic Würzburg, Würzburg, Germany.
Comprehensive Heart Failure Centre, University Clinic Würzburg, Würzburg, Germany.
Basic Res Cardiol. 2024 Apr;119(2):261-275. doi: 10.1007/s00395-024-01035-3. Epub 2024 Mar 4.
Myocardial infarction (MI) induces the generation of proinflammatory Ly6C monocytes in the spleen and the recruitment of these cells to the myocardium. CD4 Foxp3 CD25 T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4 T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4 T-cell deficient animals. Conventional CD4 T-cells promoted myelopoiesis in vitro by cell-cell-contact and paracrine mechanisms, including interferon-gamma (IFN-γ) signalling. Depletion of regulatory T-cells enhanced myelopoiesis in vivo, as evidenced by increases in progenitor cell numbers and proliferative activity in the spleen 5 days after MI. The frequency of CD4 T-cells-producing factors that promote myelopoiesis increased within the spleen of Treg-depleted mice. Moreover, depletion of Tregs caused a proinflammatory bias in splenic Ly6C monocytes, which showed predominantly upregulated expression of IFN-γ responsive genes after MI. Our results indicate that conventional CD4 T-cells promote and Tregs attenuate splenic myelopoiesis and proinflammatory differentiation of monocytes.
心肌梗死（MI）会在脾脏中产生促炎 Ly6C 单核细胞，并将这些细胞募集到心肌中。CD4 Foxp3 CD25 T 细胞（Tregs）通过诱导心肌单核细胞来源的巨噬细胞产生促愈合分化状态，促进心肌梗死后的愈合过程。我们旨在研究 CD4 T 细胞对脾脏髓样细胞生成和单核细胞分化的影响。我们在小鼠中诱发 MI，并发现 CD4 T 细胞缺陷动物的 MI 诱导的脾脏髓样细胞生成被阻断。常规 CD4 T 细胞通过细胞间接触和旁分泌机制，包括干扰素-γ（IFN-γ）信号转导，促进体外髓样细胞生成。在 MI 后 5 天，调节性 T 细胞耗竭增加了体内祖细胞数量和脾脏增殖活性，从而增强了体内髓样细胞生成。在 Treg 耗竭小鼠的脾脏中，促进髓样细胞生成的 CD4 T 细胞产生因子的频率增加。此外，Tregs 的耗竭导致脾脏 Ly6C 单核细胞中出现促炎偏向，MI 后其 IFN-γ 反应基因的表达主要上调。我们的结果表明，常规 CD4 T 细胞促进脾脏髓样细胞生成和 Ly6C 单核细胞的促炎分化，而 Tregs 则减弱这种作用。
