白介素25对表皮屏障功能的作用机制及其调控对抗原诱导特应性皮炎模型的影响

Epidermal barrier defect, Th2 cytokines inflammation, and innate immune abnormalities including epidermal keratinocytes all contribute to the mechanism of atopic dermatitis; while the gene-environment interactions leading to the development of the disease are only partially understood. Keratinocytes are a target for diverse stimuli such as allergens, infections and epidermal mechanical disruption. Keratinocytes activation results in the secretion of cytokines including IL-25, which can drive Th2 response. New studies show IL-25 could down-regulate filaggrin synthesis in primary keratinocytes in vitro and thereby may provide a link between the inflammatory reaction and impaired skin barrier function. In this study, we aim to investigate the role and pathways of IL-25 on the keratinocyte differentiation and epidermal barrier function by human organotypic skin model in vitro and animal model in vivo. The effect of IL-25 on epidermal barrier function will also be studies in different genetic background. Through antigen-induced atopic mouse model, we will further investigate the influence of IL-25 regulation on the development of the model, and may develop new insight on therapy and prevention of atopic dermatitis.

特应性皮炎为遗传因素与环境因素交互作用性疾病，表皮屏障功能障碍、Th2细胞因子优势的炎症模式、以及包括表皮角质形成细胞在内的天然免疫功能异常等均参与其发病，但具体机制仍不明确。抗原、感染、表皮屏障破坏等可刺激角质形成细胞产生白介素25（IL-25），进而促进Th2细胞分化及Th2细胞因子产生。同时有研究提示IL-25可能导致表皮屏障功能异常，推测IL-25在特应性皮炎的发病中可能起到了重要的桥梁作用。本课题拟利用体外人器官化皮肤及动物模型研究IL-25对角质形成细胞终末分化及表皮屏障功能的影响及其调控通路；利用动物实验研究不同遗传背景下IL-25对表皮屏障功能的影响，以深入探讨其在特应性皮炎发病中的作用及机制；并采用外来抗原诱导小鼠建立特应性皮炎模型，研究调控IL-25对该模型的影响，为特应性皮炎防治提供新的思路。