自发特应性皮炎人源化小鼠模型的建立及在抗体免疫治疗的应用

特应性皮炎(Atopic Dermatitis，AD)是最常见的慢性皮肤病之一，其中重度AD缺乏有效且副作用小的治疗方法。作为新兴研究热点，靶向炎症因子的抗体免疫治疗可有效缓解中重度AD病症，具有重大临床价值。然而，人与小鼠免疫系统存在不少差异，使传统小鼠模型难以发现新的治疗靶点，也无法作为治疗性抗体的临床前评价模型。项目组通过在重度免疫缺陷鼠皮肤特异性表达鼠源细胞因子TSLP，并移植人造血干细胞重建免疫系统，构建自发AD人源化小鼠模型，可体内直接评估临床前抗体药物。本项目拟通过自发AD人源化小鼠模型，结合临床样本探索AD发生机制，并通过分析AD发病过程中免疫细胞亚群及炎症因子的动态特征，发现并体内评估可用于抗体治疗的新靶点。

Atopic dermatitis (AD) is common chronic skin inflammation with numbers of cases increasing every year. Options to treat moderate or severe AD are limited and often accompanied by adverse effects. Immunotherapy, such as antibodies targeting inflammatory cytokines or their receptors, has emerged in recent years to treat AD with great promise. However, current animal models are not suitable for the evaluation of the efficacy and toxicity of these human antibodies due to species specificity. To solve this issue, we utilized severely immunodeficient mouse strains to establish humanized mice by transplanting human hematopoietic stem cells. Spontaneous AD developed exclusively in humanized mice with skin-specific.expression of mouse TSLP. Based on this AD humanized mouse model, we propose to study the mechanism which drives AD phenotypes in patients and humanized mice; to characterize the kinetics of immune subsets and inflammatory cytokines during disease progression; to explore and evaluate potential targets for antibody immunotherapy against AD.