Τ17细胞介导银屑病皮肤炎症性病变形成中CD30L/CD30信号转导的保护性作用机制研究

银屑病是一种常见的、免疫系统介导的慢性炎症性皮肤病，其发病机制尚不清楚。目前研究发现，T17细胞及其细胞因子在银屑病变形成中起关键作用。以往研究证明，CD30L/CD30信号对肠黏膜Th17和IL-17A+Vγ6+γδT细胞的分化及功能具有重要调节作用。但迄今为止，有关T17细胞介导银屑病皮肤炎症病变形成中CD30L/CD30作用机制的研究鲜有报道。本项目前期研究发现，CD30L基因敲除导致小鼠对银屑病易感性显著升高，并伴随Vγ4+γδT细胞皮损组织浸润及细胞因子分泌增加。结果提示CD30L/CD30信号在银屑病发病机制中具有潜在的保护性作用。因此，本项目将通过对CD30L-/-小鼠银屑病模型及临床患者样本的研究，探讨Τ17细胞介导银屑病皮肤炎症性病变形成中CD30L/CD30信号转导的保护性作用机制，评价以其为靶点的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开辟新思路。

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders characterized by hyperproliferative keratinocytes and massive infiltration of leukocytes. Although the pathogenesis of psoriasis is not fully understood, there is growing evidence that T17 cell (including mainly Th17 and γδ T cell) and the related cytokines, such as IL-17A and IL-22, play critical roles in disease development. In our recent studies, it has been demonstrated that CD30L/CD30 signaling plays critical roles in the differentiation, maintenance and functional regulation of Th17 and IL-17A-producing Vγ6+ γδ T cell in mucosa-associated tissues. But so far, there is few relevant report about CD30L/CD30 signal and skin immune responses. In this study, we have already been found that CD30L gene knockout lead to the susceptibility to psoriasis significantly increased in mice, accompanying massive infiltration of inflammatory cells, such as Vγ4+ γδT cells, and increasing production of inflammatory cytokines. These results suggest that CD30L/CD30 signaling plays a potential protective role in the pathogenesis of psoriasis in mice. Therefore, in this study, we plan to investigate the regulatory role of CD30L/CD30 signaling in skin immune response during the development of psoriasis, elucidate the molecular mechanism of its protective effect, using CD30L-/- mice to induce different types of psoriasis model and the skin samples from psoriasis patients, and then evaluate the therapeutic effect of monoclonal antibody targeting CD30L/CD30 signal on psoriasis. This work will clarify the potential roles of CD30L/CD30 signaling in the pathogenesis of psoriasis and provide an important theoretical basis for psoriasis immune therapy.