CHI3L1/IL-13Rα2在银屑病皮肤炎症应答中的作用机制研究

银屑病是由免疫系统功能紊乱所引起的皮肤慢性炎症性自身免疫性疾病，其发病机制尚不清楚。新近研究发现几丁质酶-3样蛋白1（CHI3L1）及其受体IL-13Rα2在多种免疫系统相关疾病病变形成中起重要作用。有研究认为CHI3L1是反应银屑病症状程度的重要生物标志物，然而其作用机制尚未阐明。本项目前期通过全基因组表达谱芯片检测，发现小鼠银屑病皮肤组织内Chi3l1基因表达显著上调，验证实验证明皮损组织内CHI3L1蛋白和mRNA，以及血清CHI3L1水平均显著增加，而且抗体中和CHI3L1可明显改善小鼠银屑病皮肤炎症症状。前期结果提示，CHI3L1/IL-13Rα2在银屑病发病机制中发挥重要的促炎作用。因此，本项目将对银屑病动物模型及临床样本开展深入研究，阐明CHI3L1/IL-13Rα2促银屑病皮肤炎症应答的分子机制，并评价靶向性单克隆抗体对银屑病的疗效，为临床银屑病免疫疗法的开发提供新思路。

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders characterized by hyperproliferative keratinocytes and massive infiltration of leukocytes. However, the pathogenesis of psoriasis is not fully understoodIts. Recently, it has been found that CHI3L1/IL-13Rα2 plays an important role in the pathogenesis of multiple autoimmune diseases. Moreover, the level of serum CHI3L1 is considered to be one of the important biomarkers of psoriasis, but the regulation mechanism of CHI3L1 in the pathogenesis of psoriasis has not been elucidated. In the early stage of the project, the gene expression level of Chi3l1 was significantly increased in the skin lesions of psoriasis mice through the screening of differential genes by the expression of mouse whole genome microarrays. Further experiments confirmed that the expression of CHI3L1 protein and mRNA in the inflammatory lesions of skin and the level of CHI3L1 protein in serum were significantly increased. Antibody neutralization of CHI3L1 can improve the inflammatory symptoms of psoriasis skin in mice. The results suggest that CHI3L1/IL-13Rα2 may play an important pro-inflammatory role in the pathogenesis of psoriasis. Therefore, in this study, we plan to carry out in-depth research on psoriasis animal model and clinical samples, clarify the cellular and molecular mechanism of CHI3L1/IL-13Rα2 promoting the inflammatory response of psoriasis skin lesions, evaluate the efficacy of targeted monoclonal antibodies on psoriasis, and provide an important theoretical basis for psoriasis immune therapy.