Effect of mesenchymal stem cells on airway inflammation in asthmatic mice depleted of CD4+CD25+regulatory T cells

Zhuansun Yong-xun; Zhang Wei; Du Yu-mo; Ran Pi-xin; Chen Rui; Lin Lin; Li Jian-guo

doi:10.3969/j.issn.2095-4344.2017.05.015

Abstract：BACKGROUND:Mesenchymal stem cel s have an immunoregulatory capacity to suppress the airway inflammation of asthmatic mice, but the mechanism remains unclear. Our preliminary studies indicated that mesenchymal stem cel s can upregulate the CD4+CD25+regulatory T cel s (Treg) of the asthmatic mice. OBJECTIVE:To study the effect of mesenchymal stem cel s on the airway inflammation in asthmatic BALB/c mice depleted of CD4+CD25+Treg. METHODS:Forty BALB/c mice were randomly divided into five groups:normal control group (group A), asthmatic group (group B), asthmatic group depleted of CD4+CD25+Treg (group C), mesenchymal stem cel s group (group D), and asthmatic group depleted of CD4+CD25+Treg and administrated with mesenchymal stem cel s (group E). Except group A, mice in the other groups were sensitized and chal enged by ovalbumin to establish asthma models. In group C and group E, each mouse was treated with anti-CD25+monoclonal antibody to deplete CD4+CD25+Treg. In group D and group E, mice were intravenously administered with 0.2 mL mesenchymal stem cel s 1×109/L) at 10 days after sensitization. At 24 hours after the final activation, the number of CD4+CD25+Treg in the peripheral blood was detected by flow cytometry. The total cel number of inflammatory cel s in the bronchoalveolar lavage fluid, and the number of eosinophils, lymphocytes and neutrophils were counted to analyze the degree of inflammation of the airway together with pathological observation. RESULTS AND CONCLUSION:(1) The proportion of CD4+CD25+Treg in peripheral lymphocytes was ranged as fol ows:group B<group D<group A (P<0.01). (2) Number of inflammatory cel s in the bronchoalveolar lavage fluid:Regarding the total cel number and the number of eosinophils in the bronchoalveolar lavage fluid, ranking was as fol ows:groups B, C, D, E were significantly higher than group A (P<0.01), group C was significantly higher than group B ( P<0.01), group D was significantly lower than group B (P<0.01), group E was significantly lower than group C (P<0.01). (3) Pathological observation of the lung:Mesenchymal stem cel s could significantly inhibit the airway inflammation of asthmatic mice. The asthmatic mice appeared to have severer airway inflammation when CD4+CD25+Treg were depleted from the peripheral blood. However, mesenchymal stem cel s could also significantly inhibit the airway inflammation of asthmatic mice depleted of CD4+CD25+Treg. Taken together, our data indicate that mesenchymal stem cel s can significantly inhibit the airway inflammation of asthmatic mice depleted of CD4+CD25+Treg.