ABSTRACT
BACKGROUND: Imbalance of Th1/Th2 immune response is an crucial pathophysiological manifestation of asthma, but recent studies have proved that asthma also has a close correlation with the imbalance of Foxp3+Treg/Th17. Accumulating evidence indicate that the immunoregulatory capacity of mesenchymal stem cells are mainly related to exosomes secreted by the cells. OBJECTIVE: To observe the effect of bone marrow mesenchymal stem cell exosomes on Foxp3+Treg cells, Th17 T cells and airway inflammation of asthmatic mice as well as cytokines in the bronchoalveolar lavage fluid. METHODS: Twenty-seven BALB/c mice of SPF grade were randomly divided into three groups: normal control group, asthmatic model group, and exosomes group. Except the normal control group, each mouse in the other groups was sensitized by ovalbumin to establish asthma models. In the exosomes group, each mouse was intravenously administrated with exosomes at 21 days of sensitization. At 24 hours after the final administration of ovalbumin, the proportion of Foxp3+Treg and Th17 in the sleep of asthmatic mice as well as the expression of CTLA-4 and PD-1 in Foxp3+Treg cells were detected by flow cytometry. The total number of inflammatory cells, and the number of eosinophils, lymphocytes, monocytes and neutrophils in the bronchoalveolar lavage fluid were counted to analyze the degree of airway inflammation in the combination with pathological observation. We also detected the expression of interleukin-4,5,13,10,17 and interferon-γ in the bronchoalveolar lavage fluid as well as p27kip1in CD4+T cells. RESULTS AND CONCLUSION: (1) The proportion of Foxp3+Treg in splenic lymphocytes and the CTLA-4 and PD-1 expression in Foxp3+Treg were significantly higher in the exosomes group than the asthmatic model group (P < 0.01). (2) The proportion of Th17 in splenic lymphocytes was ranked as follows: asthmatic model group > exosomes group > normal control group (P < 0.01). (3) The total number of inflammatory cells and the number of eosinophils, lymphocytes, neutrophils and monocytes in the bronchoalveolar lavage fluid were ranked as follows: asthmatic model group > exosomes group > normal control group (P < 0.01). (4) Pathological observation of the lung showed that the asthmatic mice appeared to have severest airway inflammation. However, mesenchymal stem cell exosomes could significantly alleviate the airway inflammation. (5) The detection of cytokines in the bronchoalveolar lavage fluid showed that levels of interleukin 13 and interleukin 17 were significantly reduced (P < 0.05, P < 0.01), while the level of interleukin 10 increased (P < 0.01). (6) The p27kip1expression in the CD4+T cells was obviously higher in the exosomes group than the asthmatic model group. In conclusion, exosomes from bone marrow mesenchymal stem cells can reverse the imbalance of Foxp3+Treg/Th17 and significantly inhibit the airway inflammation in asthmatic mice.