MDSCs Aggravate the Asthmatic Progression in Children and OVA-Allergic Mice by Regulating the Th1/Th2/Th17 Responses

BACKGROUND: Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice. METHODS: The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN-γ levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN-γ in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot. RESULTS: In clinical trials, the levels of IL-12, IFN-γ, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN-γ levels reduced, illustrating that MDSCs exacerbated asthma. CONCLUSION: Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response.