IgE活化抗原递呈细胞IL-17信号通路在银屑病中的作用及机制

我们发现银屑病患者外周血IgE水平增高，FcεRI在皮损天然免疫细胞上高表达，IL-17拮抗剂成功治疗可下调IgE和FcεRI的表达，粉尘螨抗原可诱导银屑病患者外周血CD32+APCs产生IL-17，提示IgE-FcεRI可能通过作用于APC而参与银屑病，然而确切的作用和机制尚不明确。我们提出假说认为抗原可通过活化IgE敏化的CD32+APCs细胞，辅助T细胞向Th7/Th1方向分化，参与银屑病的发生。本研究拟通过NP-IgE特异性激活APCs上IgE/FcεRI通路，分析对APCs产生促炎细胞因子的影响，分析粉尘螨抗原诱导APCs产生IL-17的机制，分析FcεRI活化的APCs对效应T细胞的影响及IL-17在炎症中的放大作用，并通过hu-FcεRI转基因小鼠，分析IgE/FcεRI通路活化对咪喹莫特银屑病模型的影响。本研究将揭示IgE在银屑病发病中的作用机制，提供银屑病治疗的新靶点。

Our study showed that serum total IgE level was increased in psoriasis, and high expression of FcεRI on innate cells in skin lesions of psoriasis. Successful therapy of IL-17 inhibitor can degrade the expression of IgE and FcεRI. House dust mite antigen can induce CD32+APCs to produce IL-17 in psoriasis, which indicates IgE-FcεRI pathway might be involved in psoriasis by acting on APCs. However, the exact mechanism remains to be elucidated. We propose that antigen can activate IgE sensitized CD32+APCs, and help T cells differentiated to Th17/Th1 cells, involved in the development of psoriasis. This study will analyze the mechanism and effect on the proinflammatory cytokines produced by APCs by NP-IgE specificly activating IgE/ FcεRI pathway, and analyze the mechanism of house dust mite antigen inducing APCs to produce IL-17, and analyze the effect of FcεRI activated APCs on the differentiation of effective T cells and the role of IL-17 on the amplification of inflammation. Moreover, we will analyze the effect of activating IgE / FcεRI pathway on imiquimod induced psoriasis model. Our study will shed light on the role of IgE in the pathogenesis of psoriasis, and will provide a new target for treating psoriasis.