针刺通过阻断Kv1.3通道抑制效应记忆T细胞活化减轻银屑病复发的机制研究

银屑病尚无法根治，其易复发的特征是目前临床治疗的重大难点。效应记忆T细胞（TEM）的活化是导致银屑病复发的重要原因，而阻断电压门控钾通道1.3（Kv1.3）可抑制TEM细胞的活化，其机制与调控PP2A/AKT/mTOR通路紧密相关。我们前期研究证实，针刺可显著减轻小鼠银屑病皮损的复发，其作用与抑制TEM细胞活化和下调Kv1.3通道表达相关。由此我们推测针刺是通过阻断Kv1.3通道调控PP2A/AKT/mTOR通路，进而抑制TEM细胞的活化起到减轻银屑病复发的作用。本项目拟采用人源化小鼠银屑病复发模型和体外细胞分选、体内外基因重组、过继传输等技术，探讨针刺抑制TEM细胞活化减轻银屑病复发的分子机制。本项目将从“阻断Kv1.3 通道-抑制TEM细胞活化-减轻免疫性炎症”的角度，阐释针刺减轻银屑病复发的科学内涵，为其临床应用提供科学依据，也为解决银屑病复发这一临床难点问题提供新思路。

There is no cure for psoriasis so far, and its characteristic of easily relapse has been the major difficulty in clinical treatment. The activation of effector memory T cells (TEM) is a major cause of the pathogenesis of psoriasis relapse. While blocking voltage-gated potassium channel 1.3 (Kv1.3) can inhibit the activation of TEM cells, which is closely related to regulation of PP2A/AKT/mTOR pathway. Our previous study confirmed that acupuncture significantly alleviated the relapse of skin lesions in psoriatic mice, which was related to inhibition of TEM cells activation and downregulation of Kv1.3 channel expression. Therefore, we speculate that acupuncture regulates PP2A/AKT/mTOR pathway by blocking Kv1.3 channel, thereby inhibiting the activation of TEM cells and alleviating the relapse of psoriasis. In this study, we will investigate the molecular mechanism of acupuncture on inhibiting the TEM cells activation and alleviating the relapse of psoriasis through psoriasis relapse model of humanized mouse, in vitro cell sorting, in vitro and in vivo genetic recombination, adoptive transfer and other techniques. This study will elucidate the scientific connotation of acupuncture in alleviating the relapse of psoriasis from the perspective of “blocking Kv1.3 channel-inhibiting TEM cells activation-reducing the immune inflammation”, providing a scientific evidence for its clinical application and a new approach for solving the relapse of psoriasis.