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首页> 外文期刊>Allergy >Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells.
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Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells.

机译：同种异体间充质干细胞通过诱导鼠类调节性T细胞来预防过敏性气道炎症。

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BACKGROUND: Adult bone marrow-derived mesenchymal stem cells (MSC) possess potent immune modulatory effects which support their possible use as a therapy for immune-mediated disease. MSC induce regulatory T cells (T(reg)) in vitro although the in vivo relevance of this is not clear. OBJECTIVE: This study addressed the hypothesis that adult bone marrow derived-MSC would prevent the pathology associated with allergen-driven airway inflammation, and sought to define the effector mechanism. METHODS: The influence of allogeneic MSC was examined in a model system where T(reg) induction is essential to prevent pathology. This was tested using a combination of a model of ovalbumin-driven inflammation with allogeneic MSC cell therapy. RESULTS: Systemic administration of allogeneic MSC protected the airways from allergen-induced pathology, reducing airway inflammation and allergen-specific IgE. MSC were not globally suppressive but induced CD4(+) FoxP3(+) T cells and modulated cell-mediated responses at a local and systemic level, decreasing IL-4 but increasing IL-10 in bronchial fluid and from allergen re-stimulated splenocytes. Moderate dose cyclophosphamide protocols were used to differentially ablate T(reg) responses; under these conditions the major beneficial effect of MSC therapy was lost, suggesting induction of T(reg) as the key mechanism of action by MSC in this model. In spite of the elimination of T(reg) , a significant reduction in airway eosinophilia persisted in those treated with MSC. CONCLUSION: These data demonstrate that MSC induce T(reg) in vivo and reduce allergen-driven pathology. Multiple T(reg) dependent and independent mechanisms of therapeutic action are employed by MSC.
机译：背景：成年骨髓源性间充质干细胞（MSC）具有有效的免疫调节作用，支持其可能用作免疫介导疾病的治疗方法。 MSC体外诱导调节性T细胞（T（reg）），尽管其在体内的相关性尚不清楚。目的：这项研究提出了一个假设，即成年骨髓源性MSC可以预防与变应原引起的气道炎症相关的病理，并试图确定其效应机制。方法：在模型系统中检查了同种异体MSC的影响，其中T（reg）诱导对于预防病理至关重要。使用卵清蛋白驱动的炎症模型与同种异体MSC细胞疗法的组合进行了测试。结果：异体间充质干细胞的全身给药可保护气道免受过敏原诱发的病理影响，减少气道炎症和过敏原特异性IgE。 MSC不能整体抑制，但可以诱导CD4（+）FoxP3（+）T细胞并在局部和全身水平调节细胞介导的反应，降低支气管液中IL-4但增加IL-10，并由变应原重新刺激的脾细胞中。使用中等剂量的环磷酰胺方案差异消融T（reg）反应。在这些条件下，失去了MSC治疗的主要有益作用，表明在该模型中诱导T（reg）是MSC作用的关键机制。尽管消除了T（reg），但用MSC治疗的患者气道嗜酸性粒细胞减少仍然存在。结论：这些数据表明，MSC可在体内诱导T（reg）并减少过敏原驱动的病理。 MSC采用了多种依赖于T（reg）的和独立的治疗作用机制。

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