Establishment Of Th17-mediated Mouse Allergic Asthma Model With Increased Neutriophils Around Airways2

Background and Purposes:In allergic asthma is an allergic associated disease, charactered byairway hyperreactivity (AHR), perivasucular and peribronchial eosinophilicinfiltrates, goblet cell hyperplasia, airway remodeling and so on. Immunesystem disorder is one of numerous mechanisms. Activated CD4~+cellsthought to be the major cause of disease, especially Th1/Th2cells imbalanceis the main mechanism. Previous studies have demonstrated that, activationof CD4~+Th2cells increased around can cause airway and vascularinfiltration of eosinophils, Th1/Th2immune response imbalance as the maincause of asthma is also widely used in clinical and basic research. Th17cellwhich is the main source of IL-17is a new member of the CD4~+T cell familyand have the function of raised, chemotaxis neutrophil invasion ofpathogenic sites, play a positive role in host defense. Recently, bothdomestic and foreign scholars found higher levels of IL-17in the BALF andserum in asthma patients. In severe asthma patients and glucocorticoid treatment resistance patients whose airway infiltrated inflammation cellsmainly are neutrophils, the proportions of eosinophils are decreased even tono existence. The enhancement of the Th17immune response may be a newmechanism for the pathogenesis of asthma. Therefore, this study intends toestablish a new murine asthma model charactered by the airway infiltratedby neutrophils, and explore the role of Th17immune response.Methods:1. Establish the typical murine asthma model charactered by highlevels of eosinophils proportion infiltrated in airways throughintraperitoneal sensitization. Identify it.2. Dendritic cells incubated with ovalbumin for night, then co-culturewith na ve T cells, and addition LPS to stimulate polarization. Identifyeffective CD4~+cells.3. Improve the traditional modeling method by increased airwaysensitization of instillation LPS+OVA, identification of new model fromairway hyperreactivity, polarization of na ve T cells in lung tissue,bronchoalveolar lavage fluid (BALF) inflammatory cells classification,histopathological study and so on.Results:1. The traditional murine asthma model established successfullycharactered by AHR, perivasucular and peribronchial inflammation cellsinfiltrated, high levels of eosinophilic proportion in BALF cells, high levels of IL-5in BALF supernatant.2. Co-culture results demonstrated that, OVA-DC could stimulate thena ve T cells polarizing to Th2cells; and LPS-OVA-DC could stimulate thena ve T cells polarizing to Th17cells.3. Established a new murine asthma model by improving traditionalmethods by addition airway sensitization with LPS+OVA: remarkableairway hyperresponsiveness; airway and perivascular infiltration ofinflammatory cells; high levels of neutrophilic proportion of BALF cellsclassification; cytokines IL-17, IL-8, and TNF-α increased moresignificantly.Conclusions:1. LPS can change antigens those presented by OVA-DC, theninfluence the differentiation of na ve T cells.2. Increased airway sensitization by dropping LPS+OVA, can makethe na ve T cells polarizing to Th17cells, then secrete IL-17to promote theinfiltration of neutrophils in peripheral airway and vascular in lung tissuesof asthmatic mice, and eventually change some pathological features.