特应性皮炎(AD)患者常伴有血清总IgE和(或)特异性IgE增高，但IgE在AD中的确切作用尚不明确。IgE增高也常见于红斑狼疮和银屑病患者；我们发现Th1、Th2、Th17型皮肤炎症小鼠模型均具有高水平IgE，这些IgE具有识别自身抗原、极少可变区基因突变的天然抗体特征，负向调控树突状细胞(DC)应答。我们提出假说认为IgE是AD皮肤炎症的结果而不是原因，AD患者的IgE主要是天然IgE(nIgE)，nIgE可能通过DC负向调控AD免疫应答。本研究拟深入分析AD患者及AD小鼠模型nIgE的特异性、亲和力等特征，免疫组库技术分析nIgE编码基因，利用DC特异性表达FcεRI的CD11c-FcεRI小鼠研究nIgE-FcεRI对DC功能的影响及在AD中的作用，利用单细胞测序技术研究产生nIgE的B细胞分化及其调控机制。本研究预期将揭示IgE在AD中的确切作用和产生机制，建立AD防治的新策略。

Most of the patients with atopic dermatitis (AD) have elevated level of serum IgE, which was thought to be produced via Th2 immune response and promote the skin inflammation of AD. We find that there are also elevated level of serum IgE in non-atopic skin inflammatory diseases, e.g. psoriasis and mouse modes of Th1, Th2 and Th17 type skin inflammation. These IgE are characteristics of natual antibody, and negatively regulate the immune response of dendritic cells (DC). We hypothesize that IgE is the result, but not the cause, of the skin inflammation of AD, the majority of IgE of AD patients are natural IgE (nIgE), and mainly play a regulatory role in the immune response of AD through DC. In the present proposal, we plan to analyze the antigen specificity and encoding genes of nIgE in AD patients and mouse model of AD, to study the role of nIgE-FcεRI through dendritic cells in the pathogenesis of AD, and to explore the differentiation mechanism of nIgE-producing B cells by using single-cell RNA sequencing. The present proposal would uncover the exact function of IgE in the pathogenesis of AD, and to develop new strategies for the prevention and treatment of AD.