银屑病是Th1细胞介导的慢性炎症性疾病，在Th1细胞归巢至皮肤过程中真皮微血管内皮细胞表达的趋化因子起十分重要的作用。本项目在完成了系列探讨CKLF-1在银屑病中的表达、功能和机制研究基础上，进一步研究CKLF-1分子C端衍生肽C19作为拮抗剂对银屑病皮损CKLF-1等趋化因子功能及其与受体相互作用的干预调节机制。首先检测CCL17、CCL22及CX3CL1在银屑病皮损内皮细胞的表达，观察其受体CCR4及CX3CR1在皮损及外周血淋巴细胞的表达；通过体外细胞培养，观察CKLF-1-C19对CKLF-1诱导的Th1细胞的趋化活性及对真皮微血管内皮细胞和角质形成细胞增殖的调节，可能的信号传导通路；构建CKLF-1转基因小鼠，建立银屑病实验动物模型（人银屑病皮损-SCID鼠移植模型），经CKLF-1-C19多肽和抗CCR4单抗处理后观察银屑病皮损改善情况。为研发自主知识产权治疗药物提供科学依据。

Psoriasis is a chronic inflammatory disease induced by Th1 cells. Chemokines presented by dermal microvascular endothelial cells play an crucial role in recruiting T cells to the skin. Based on the research of expression, function and mechanism of a novel chemokine CKLF-1 in psoriasis, we intend to further study the regulation mechanism of its C terminal derived peptide C19 as antagonist to CKLF-1 and other chemokines in psoriasis and interaction with receptors. First, testing the expression of CKLF-1, CCL17, CCL22 and CX3CL1 in endothelial cell of psoriasis lesion and the expression of receptors CCR4 and CX3CR1 in psoriasis lesion and peripheral blood lymphocyte. Then we observe the CKLF-1-C19 effect on the chemotactic activity of CKLF-1 attracting Th1 cells and the regulation influence on the proliferation of microvascular endothelial cells and keratinocytes. Establishing psoriasis experimental animal model (human psoriasis lesion-SCID mice transplanted model) and CKLF-1 encoding gene transfer mice, we applied CKLF-1-C19 peptide or CCR4 monoclonal antibody to them, observing the improvement of psoriasis lesion. For research new anti-inflammatory drug aiming at chemokine, providing scientific basis and idea.