临床中普遍发现长期持续外用糖皮质激素（glucocorticoid, GC）可导致银屑病复发，真皮γδT细胞的增殖趋化被认为在其中作用重大，但具体分子机制仍不明。我们的前期研究发现促炎症消退介质（SPMs）在银屑病中发挥着抗增殖抗炎效应，且可下调真皮γδT细胞数量，同时我们发现外用GC能下调SPMs的含量。本项目在此基础上，拟在细胞、动物模型及临床标本多个层面，运用病毒转染、流式细胞术及HPLC-MS等技术，阐明GC可能通过抑制SPMs关键酶-ALOX15的表达从而下调SPMs的合成，进而IL-23、IL-1β、CCL2、CCL20等炎性因子及趋化因子不能得以有效抑制，导致外周淋巴结中γδT细胞增殖通过血液向皮损区趋化，释放IL-17及IL-22等炎性因子，形成炎症的循环反馈，诱发银屑病复发的分子机制。本项目有助于为银屑病复发提供新的理论基础，对临床指导患者合理外用GC及新药开发提供指导。

It has been widely found that consistently topical glucocorticoid (GC) therapy can lead to the recurrence of psoriasis in clinical practice. The proliferation and chemotaxis of dermal γδT cells are considered to play a significant role in it, but the specific molecular mechanism is still unknown. Our previous work found that specialized proresolving mediators (SPMs) play an anti-proliferation and anti-inflammatory effect in psoriasis, and can down-regulate the number of dermal γδT cells, and we also found that the content of SPMs could be down-regulated by topical GC. Based on the previous works, we will use virus transfection, flow cytometry and HPLC-MS technology and other methods in multiple levels including cells, animal models and clinical specimens, to study the possible molecular mechanism that GC inhibit ALOX15 – the key enzymes in metabolism of SPMs to down-regulate the expression of SPMs, then the inflammatory cytokines and chemokines including IL-23、IL-1β、CCL2、CCL20 cannot be effectively restrain, eventually leading to peripheral drainage lymph nodes γδT cells proliferation, the γδT cells chemotaxis to the lesion area by blood pathway and release inflammatory factors such as IL-17 and IL-22, causing the inflammation circular feedback, and then induce the recurrence of psoriasis. This project will help provide a new theoretical basis for psoriasis recurrence, and provide some guidance for clinical patients with reasonable topical GC and the development of new medicines.