CARD9调控IL-23/Th17信号通路介导银屑病发生发展的机制研究

银屑病是一种以角质形成细胞过度增殖和异常分化为主要特征的慢性炎症性皮肤病，具体发病机制不明。胱天蛋白酶募集域蛋白9(CARD9)存在于人体多种组织中（尤其高表达于树突状细胞中），被证实与自身免疫性疾病的发生明确相关。CARD9介导DCs释放的炎性介质可促进Th17细胞极化，且与皮肤损伤修复有关，而CARD9在银屑病中的作用及机制尚无报道。我们前期研究发现寻常型银屑病患者皮损CARD9表达较正常对照显著增加，CARD9敲除小鼠经咪喹莫特诱导的银屑病模型皮损严重程度、表皮增生程度及淋巴结中Th17细胞数量都较野生型明显降低。由此，我们提出CARD9调控IL-23/Th17信号通路介导角质形成细胞异常增殖，进而影响银屑病皮损形成的全新假说。本课题拟通过体内外实验阐明CARD9调控银屑病角质形成细胞异常增殖凋亡的分子机制及其对小鼠银屑病样皮损形成的影响，深入探讨CARD9在银屑病发病机制中的作用。

Psoriasis is a disease whose pathogenesis has not been fully elucidated, abnormal proliferation and differentiation of keratinocytes play an important role in it. Caspase recruitment domain protein 9(CARD9) exists in various tissues (especially highly expressed in dendritic cells) of the human body. In recent years, CARD9 has been found to be related to the occurrence of autoimmune diseases. The inflammatory mediators released from CARD9-induced DCs greatly prefer the polarization of Th17 cell responses. CARD9 also attributed to skin damage repair. However, whether CARD9 is involved in the occurrence and development of psoriasis has not been reported. Our previous experiments found that the expression of CARD9 was significantly increased in psoriasis patients’ skin lesions, the severity of psoriasis-like skin lesions, histopathological epidermal hyperplasia, and number of lymph node Th17 cells in CARD9 knockout mice were significantly reduced after imiquimod treatment. Therefore, we propose the hypothesis that CARD9 regulates IL-23/Th17 signaling pathway and mediates abnormal proliferation of keratinocytes, then the formation of psoriasis. Our project will elucidate the role and molecular mechanism of CARD9 in regulating the abnormal proliferation and apoptosis of keratinocytes, as well as its effect on the formation of psoriasis-like skin lesions in mice through in vivo and in vitro experiments. We will conduct a thorough discussion of the role of CARD9 in the pathogenesis of psoriasis.