Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells

To cite this article: Kavanagh H, Mahon BP. Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 2011; 66 : 523–531. Abstract 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.