银屑病复发是其特征。已在构建的糖皮质激素（GC）外用于银屑病鼠的模型中观察到外用GC后皮肤IL-17和T17细胞减少，但在淋巴结中增加；停用GC复发后皮肤中IL-17和T17又复增加而淋巴结中减少；同时，具有产生IL-17和“记忆”双重功能的Vγ4+细胞在GC治疗后下降比例最低而复发时上升最高；患者外用GC治疗前后及复发时皮损RNA-seq变化与鼠相近，尤其是趋化因子变化最显著。因此，该项目以GC治疗为切入点，从皮肤记忆细胞及归巢研究银屑病复发机制：通过Tcrd-/-及Tcrα-/-鼠重复外用GC的银屑病鼠模型实验，证实记忆T细胞是αβT还是γδT；在鼠通过mannan、人通过表皮菌群研究记忆对象和记忆细胞活化的条件；Ccr2-/-及Ccr6-/-鼠与FTY720阻断实验验证趋化因子功能；患者外用GC或注射IL-17A单抗ixekizumab验证与鼠模型的相似性。以寻找预防复发的靶点。

Relapse is a characteristic feature of psoriasis. In our previous study, topical glucocorticoid (GC) was used to treat psoriatic mouse model, which we observed that IL-17 and T17 cells were both decreased with topical GC, but increased in lymph nodes; After GC withdrawal, IL-17 and T17 cells was increased in the skin, while decreased in the lymph nodes; meanwhile, with the dual function of IL-17 producing and "memory", Vγ 4+T cell number was minimally decreased after GC treatment and increased significantly during relapse; Using RNA sequencing, changes in patients skin were similar with mouse findings after GC treatment, especially change in chemokine levels were significant. Therefore, by using topical GC to treat psoriasis, we will study the mechanism of psoriasis relapse from the perspective of memory T cells and skin T cells homing: through Tcrd-/- and Tcrα-/- mice to repeat topical GC to treat psoriasis model to confirm that the cell population of memory T cells:αβT cell or γδTcell; by applying mannan in mice and altering skin microflora in patients, we purposed to investigate memory objects and conditions of memory cell activation; we will study functions of chemokines by breeding Ccr2-/- and Ccr6-/- mice to repeat topic GC treatment psoriatic mouse model and blocking T cell homing by FTY720; patients treated with topical GC or injection of IL-17A monoclonal antibody ixekizumab to mirror animal study. We aim to find new target to prevent psoriasis relapse.