真皮乳头层血管的高度迂曲扩张及通透性增高是银屑病的突出病理改变，但其机制尚不清楚。角蛋白17（K17）是银屑病角质形成细胞特异性高表达的一种角蛋白，通过活化角质形成细胞、协同趋化多种炎细胞等作用构成银屑病发病的“K17环路”机制。我们近期发现，咪喹莫特诱导的小鼠银屑病样模型皮损处微血管明显扩张并伴通透性增高，而K17敲除小鼠的银屑病表型和皮肤微血管改变均明显减轻。对银屑病患者的研究也发现皮损K17的表达与微血管扩张程度呈正相关。因此认为，K17通过活化角质形成细胞、趋化炎细胞并释放多种介质等作用，造成微血管通透性增高等异常参与银屑病发病。本课题在前期工作的基础上，利用细胞、分生、动物模型等手段分析K17对皮肤微血管通透性的调节作用，揭示调控银屑病皮肤微血管异常的关键细胞和分子事件，明确微血管通透性增高等改变在K17介导的银屑病发病机制中的意义，为研究银屑病发病机制、指导治疗提供重要依据。

Highly dilated and tortuous capillaries with increased permeability in the papillary dermis are prominent pathological characteristics of psoriasis, but of which the regulatory mechanism remains unknown. Keratin 17 (K17), a keratin highly expressed in keratinocytes specifically when psoriasis occurs, constitutes a “K17 loop” in psoriatic pathogenesis by activating keratinocytes and synergistically recruiting various inflammatory cells. We have recently discovered such noticeable dilation and elevated permeability of the micro-vessels in the skin lesion of imiquimod-induced psoriasis-like mice, while both such vascular abnormality and psoriatic phenotype were greatly alleviated in K17 knocked-out mice. What’s more important, such a positive correlation between K17 expression and severity of microvascular dilation was also seen in the lesion of psoriatic patients. Therefore, we put forward that K17 expression participates in the psoriatic pathogenesis by regulating keratinocytes’ production of various mediators and promoting the chemotaxis of several immunocytes, which contributed to the increase of capillary permeability. In the present proposal, we plan to analyze the regulatory role of K17 in the skin micro-vascular permeability using the techniques of cytology, molecular biology and animal models. We also plan to identify the key cellular and molecular events that are responsible for the elevation of skin microvasluar permeability in psoriasis. Moreover, the significance of high microvasluar permeability in the pathogenesis of K17-mediated psoriasis shall be clarified, so that they will serve as key evidence to the study of psoriatic pathogenesis and potential targets for the treatment of psoriasis.