结节性痒疹(PN)是一种剧烈瘙痒、慢性皮肤病，难以治愈。角质形成细胞(KC)过度增殖、T细胞、嗜酸粒细胞侵润，伴随PN发生和炎症慢延化过程。前期工作表明PN皮损区大麻素受体1(CB1)表达下降，角蛋白K6\K16、K17异常高表达，CB1参与调控三种角蛋白表达。K17可以刺激T细胞活化，是银屑病自身反应性T细胞识别候选靶抗原。我们提出假设：KC中的CB1表达下降时，KC自分泌相关细胞因子诱导K17高表达，活化KC，细胞增殖激活T细胞。本项目拟收集临床标本和构建的siRNA敲减和慢病毒过表达CB1的永生化角质形成细胞HaCaT细胞模型，验证CB1参与调节K17的作用和转导机制，探讨CB1诱导炎性因子调控K6/K16、K17表达并诱发KC增殖，关注CB1调控的K17表达-活化KC-T细胞的循环在PN中的作用，为PN的治疗提供新思路。

Prurigo Nodular (PN) is a severe pruritus, chronic dermatosis.Hyperkeratotic, inflammation caused by T lymphocytes, eosinophilic granulocytes and mast cells are involved in the development and chronification of PN. Keratinocytes(KCs) is hyperproliferative in PN leisons. KCs are the prodominant cell type in the epidermis, not only contribute to he physical barrier but also are involved in the "skin immune system" and modulate the local immune reaction, activated KCs express many immune-related molecules, which play important roles in local immune reaction. Our previous work showed that the expression of cannabinoid receptor 1 (CB1) in PN lesions was down-regulated, the expression of keratin K6/K16 and K17 were overexpressed in PN lesion. K17 is a 46 KD type I epithelial keratin, overexpressed in activated KCs and is closely associted with proliferation and migration of activated KCs. K17 is one of candidate target antigens recognized by psoriatic autoreactive, stimulating T cell activation, and defined as “psoriasis autoreactive cytokeratin”. Research reported that the K17/T cells/cytokine autoimmune loop was involed in psoriasis. CB1 receptor is a G-protein-coupled-receptor that is expressed at lower levels by KCs in the skin, where limits the inflammation caused by hapten-specific Tcells. In the present research work, we hypothesize that CB1, down-regulated in KC, binding by the selective agonist ACEA, induces K17 overexpression by some of autocrine-related cytokines, activates KC, induces proliferation of KCs and activates T cells. In the project, we intend to collect clinical specimens and construction of siRNA knockdown and lentivirus overexpression of CB1 immortalized keratinocytes HaCaT cell model to verify the CB1 involved in the regulation of K17 and transduction mechanisms, to explore the cytokine induced by CB1 regulating the proliferation of KCs. We will focus on the K17 expression by CB1 regulation - activation of KCs-T cell autoimmune loop in the role of PN, which may provide a new idea for the treatment of PN.