1. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells.
- Author
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Mathias LJ, Khong SM, Spyroglou L, Payne NL, Siatskas C, Thorburn AN, Boyd RL, and Heng TS
- Subjects
- Adipose Tissue cytology, Animals, Asthma etiology, Asthma immunology, Asthma pathology, Asthma physiopathology, Bone Marrow Cells cytology, Bronchial Hyperreactivity chemically induced, Bronchial Hyperreactivity etiology, Bronchoalveolar Lavage Fluid, Clodronic Acid pharmacology, Eosinophilia etiology, Eosinophilia immunology, Female, Genes, Reporter, Graft Survival, Heterografts, Humans, Immunization, Interleukin-10 biosynthesis, Interleukin-10 genetics, Lung pathology, Lymphokines biosynthesis, Lymphokines genetics, Macrophages, Alveolar drug effects, Methacholine Chloride, Mice, Mice, Inbred BALB C, Organ Specificity, Ovalbumin immunology, Ovalbumin toxicity, Species Specificity, Specific Pathogen-Free Organisms, Th2 Cells metabolism, Transduction, Genetic, Umbilical Cord cytology, Asthma therapy, Immunosuppression Therapy methods, Macrophages, Alveolar physiology, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells physiology
- Abstract
Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.
- Published
- 2013
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