补体C5a/C5aR通路促pDCs分化和功能形成介导银屑病的机制研究

银屑病(psoriasis)是一种慢性炎症性皮肤病，涉及遗传和免疫等多种因素，确切的病理机制尚不明确。咪喹莫特(Imiquimod,IMQ)诱导的银屑病皮炎小鼠是研究银屑病最常见的动物模型。利用此模型，在前期研究中我们首次发现,补体C5aR基因缺失可显著衰减小鼠银屑病病情。进一步的研究表明，与C5aR+/+小鼠相比，C5aR-/-小鼠中pDCs (plasmacytoid dendritic cells)的分化和功能均明显受损。新近的文献证实pDCs是导致银屑病免疫病理的关键细胞类型。据此推测：C5a/C5aR通路可能通过促pDCs分化与功能形成来介导银屑病的发生。本研究拟通过体内外实验明确补体C5a/C5aR通路在银屑病免疫病理中的作用；探讨该通路对pDCs分化及功能形成的调控机制。预期结果不但有助于银屑病发病机制的阐明，并且可为临床银屑病有效治疗策略的发展提供重要的理论依据。

Psoriasis is a chronic inflammatory disease of the skin，which is involved in a various factors including genetics and immune system, and there is not an effective treatment strategy for patients with psoriasis. Imiquimod (IMQ)-induced psoriasis dermatitic mice is a now widely accepted animal model in the study about the pathogenesis of psoriasis. In the previous studies, by using this successfully established mice psoriasis model, it was found that, complement C5a receptor (C5aR) gene deficiency significantly attenuated IMQ -induced scaly skin inflammation in mice. Moreover, compared with the wild type mice, both IMQ-induced plasmacytoid dendritic cells (pDCs) infiltration in local skin and the ability of bone marrow cells differentiating into pDCs was remarkably reduced in C5aR KO mice. According to the literatures, pDCs play a critical role during the pathogenesis of psoriasis. We therefore hypothesize that complement C5a/C5aR pathway mediates psoriasis development via the potentiating of pDCs differentiation and functions formation. In the present study, we will define the role of C5a/C5aR pathway in the pathogenesis of psoriasis by combination in vitro with in vivo mice experiments, and then further explore the underlying molecular mechanisms involved in C5a/C5aR pathway regulation in pDCs differentiation and function. Anticipative results will help us further clarify the precise pathogenesis of psoriasis, which may ultimately indicate effective treatment strategies for clinical patients with psoriasis.