The role of lung dendritic cells in the immunological tolerance of Der p allergen-sensitized mice

• Main Authors: Yu-Lun Cheng, 鄭宇倫
• Other Authors: Jiu-Yao Wang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/91633357945423196265

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 97 === The prevalence of allergic asthma is increasing yearly in all over the world. Exposure to aeroallergens induces sensitization of host and serious local inflammation in the lung after recurrent contacts of sensitized allergens, but the mechanism by which allergen-induced asthmatic inflammation is still unclear. In contrast, repeated low dose allergens administrations were reported to induce immune tolerance against allergen-induced airway inflammation. We hypothesized that different airborne immunogens, such as lipopolysaccharide (LPS) and house dust mite allergen (Der p extracts) act on local antigen presenting cells, such as dendritic cells in the lung (lung DCs), to induce different types of local immune response by the changes of populations and functions. Repeated low dose administrations of Der p extracts (DP) or LPS before allergen sensitization in mice may influence lung DCs to ameliorate the severity of allergen-induced asthmatic inflammation. Therefore, DP-sensitized mice were intra-tracheally pre-treated with normal saline (NS), DP, and LPS, respectively, in single or repeated low doses administrations before allergen sensitization. As compared to NS administrations, repeated low dose administrations of DP decreased DP-specific IgE in serum and total cells numbers and eosinophils infiltration in bronchoalveolar lavage fluids (BALF) in allergen- challenged sensitized mice. Airway hyperresponsiveness (AHR) and inflammation in pathology also reduced in sensitized mice with repeated low dose administrations of DP or LPS. These results show that repeated DP administration before sensitization induced well-immunotolerance, not LPS. Administration of DP before allergen sensitization demonstrated higher percentage of plasmacytoid DCs (pDCs) in lung and higher percentage of myeloid DCs (mDCs) in the mediastrial draining lymph nodes (MLN). There was no significant difference of secreted cytokines (IL-4, IL-13, IL-10, and IFN-γ) in BALF between DP and NS (controlled) pre-treated allergen sensitized mice. However, the expression levels of major histocompatibility complex (MHC) class II in lung DCs were decreased in sensitized mice with repeated DP administrations as compared with controlled sensitized mice. In summary, repeated low dose administrations of DP or LPS can reduce allergen-induced asthmatic inflammation. This mechanism may due to the effect on DCs maturation and localization, instead of the percentage change of pDCs and mDCs population.