去嗜酸性粒细胞对抗原诱导特应性皮炎模型形成的影响及机制研究

Atopic dermatitis (AD) is chronic, replasing, highly pruritic inflammatory skin disease which may followed by allergic rhinitis or allergic asthma. Recent interest in AD in china has been sparked by its increasing prevalence and the significant adverse effects of AD on patient's quality of life. In AD, the pathogenesis is not clear, but histological characteristic of AD presents as infiltration of T cells and eosonophils in dermis which highly suggested that eosinophils are involved in the pathogenesis of AD. In this study, we aimed to investigate the role of eosinophils in AD through antigen-induced AD model on eosinophil-deficient mice with different genetic background(BALB/c ?dbl-GATA and C57BL/6 IL-5-/-).We will observe the skin (skin manifestation,histology,infiltrated cells,gene differentrial expression etc.), serum (level of antibodies and cytockines etc.)and the interactions between eosinophils and T cells or mast cells, which will help clarify the mechanism of eosinophils in AD, and develop new insight on therapy or prevention.

特应性皮炎（AD）是一种慢性、复发性、瘙痒性皮肤疾病。患病率在我国逐年上升，可伴发过敏性鼻炎或哮喘，严重影响患者的生活质量。AD的发生发展机制尚未明确，组织学上真皮中T细胞和嗜酸性粒细胞浸润是AD的重要特征，强烈提示嗜酸性粒细胞参与了AD的发病。本课题拟利用不同遗传背景的嗜酸性粒细胞缺失的小鼠模型（BALB/c ?dbl-GATA和C57BL/6 IL-5-/-小鼠），通过外来抗原刺激诱导AD以及嗜酸性粒细胞回输的方法，观察小鼠皮肤（外观、组织学、浸润细胞、差异基因的表达等）和血清学（抗体水平、细胞因子等）的改变，以及嗜酸性粒细胞对T细胞、肥大细胞的影响。从而阐明嗜酸性粒细胞在AD发病中的作用及机制，为AD的预防和治疗提供新的思路。

特应性皮炎（AD）是一种慢性特发性的炎症性皮肤病。在AD的患者，嗜酸性粒细胞通常升高，但是其在AD中的作用机制尚未明确，我们利用MC903作为抗原刺激诱导嗜酸性粒细胞缺失的小鼠（BALB/c ∆dbl-GATA）AD样皮炎，研究发现： 1. 嗜酸性粒细胞在MC-903诱导的AD样皮炎中不是必要的；嗜酸性粒细胞可能是炎症过程中的一个催化因子。2. Stat3、PI3K-Akt和MAPK 信号通路在MC-903诱导的AD模型中起到主要作用。3. 嗜酸性粒细胞对Th17可能有重要的调节作用。