Inhibiting autophagy of dendritic cells meliorates asthma in mice
- Author:
Chang Wen DENG
1
Author Information
1. Department of Respiratory and Critical Care Medicine, Changhai Hospital, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Asthma;
Autophagy;
Cell proliferation;
Dendritic cells
- From:
Academic Journal of Second Military Medical University
2016;37(3):265-272
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the impact of autophagy inhibition on functions of dendritic cells (DCs) and mouse model of allergic asthma. Methods (1)BALB/c mice were divided into three groups using the random number table: asthma model group, asthma treated with autophagy inhibitor (chloroquine) group (asthma+CQ group) and control group. Mouse models in asthma group and asthma+CQ group were induced with ovalbumin (OVA); meanwhile, mice of asthma+CQ group were also treated with autophagy inhibitor CQ. Hematoxylin-Eosin (H-E) staining was used to observe the pathological changes in lung tissues of mice. ELISA, Western blotting analysis and flow cytometery were used to detect the serum OVA-specific IgE, autophagy level, and expression of surface co-stimulatory molecules and major histocompatibility complex class H (MHC H ) on lung DCs, respectively. (2)Bone marrow-derived DCs were treated with autophagy inhibitor 3-methyladenine (3MA) in vitro and the surface expression of co-stimulatory molecules and MHC H was detected. (3) We sorted CD4+ T cells from spleens of OT2 mice, then co-cultured with lung DCs from mice of different groups (T cells: DCs=1: 10), and detected the activation and proliferation of T cells with flow cytometery. Results (1) The level of OVA-specific IgE (P < 0. 05), extent of inflammatory cell infiltration in lung tissues, autophagy level in lung DCs (P<0. 05), and expression of CD86 and MHCH (P<0. 05)on lung DCs in asthma + CQ group were significantly lower than those in the asthma group. (2) 3MA treatment decreased the surface expression of CD86 and MHC" on bone marrow-derived DCs (P<0. 05). And (3) lung DCs from asthma+CQ group had lower ability for activating T cells and promoting T cell proliferation than those from the asthma group (P<0. 05). Conclusion Autophagy inhibitors can improve the pathologic condition of allergic asthma through inhibiting autophagy in DCs, down-regulating surface expression of co stimulatory molecules and MHC" on DCs, and further inhibiting the DCs-induced proliferation of T cells.
