IL-27在银屑病中调控Lag3促进Treg细胞免疫调节功能的机制研究

Psoriasis is a common chronic inflammatory skin disease. Inflammatory T cells promote the development of the disease, whereas regulatory T cells (Tregs) downregulate the inflammation. Lag3 is a transmembrane protein that can modulate the suppressive function of Treg. The expression of Lag3+Treg seems to be negatively regulating immune responses, but the mechanism of regulation is not yet clear. IL-27 is a cytokine with broad immunomodulatory effects. It has been shown that IL-27 can prevent the development of the disease by upregulating the expression of Lag3 on Treg cells during inflammatory bowel disease and autoimmune encephalomyelitis, but it is still unknown if IL-27/Lag3 axis is also involved in the development of psoriasis. Our previous study found, decreased IL-27 and IL-27rα expressions in the lesions and peripheral blood of psoriasis patients and also found that the Lag3+Treg cell number in the lesions and peripheral blood of psoriasis patients is decreased. In addition, IL-27 have alleviated the severity of IMQ-induced psoriasis, with the increase in Lag3 expression of Treg cells in spleen, but the number of FOXP3+Treg didn’t change obviously. All of above suggest that IL-27 may prevent the development of the psoriasis through regulating the function of Treg cells, but the specific regulatory mechanism is unknown. Therefore, in this project, based on our previous research we will further do some research about the regulation of IL-27 on the suppressive function of Treg cells and its regulatory mechanism through the in vitro and in vivo research system in order to provide theoretical and experimental basis on exploring a new therapeutic target of psoriasis.

银屑病是常见的慢性炎症性皮肤病，炎症性T细胞促进该病发生，而调节性T细胞（Treg）下调炎症。Lag3是一种可介导Treg抗炎作用的跨膜蛋白，Lag3+Treg含量似与炎症负相关，但调控机制未明。IL-27是具有广泛免疫调节作用的细胞因子，在炎症性肠病及自身免疫性脑脊髓膜炎中能上调Treg上的Lag3表达而延缓疾病进展，但是否参与银屑病的发展尚未知晓。我们前期研究发现银屑病患者外周血及皮损中IL-27及其受体表达下调；Lag3+Treg细胞数目减少；IL-27治疗后的银屑病模型小鼠银屑病样皮损明显减轻，脾脏中Lag3表达上调而FOXP3+Treg细胞数未见明显增加，提示IL-27可能调控Treg细胞的功能而缓解银屑病的发展，但调控机制不详。本课题将在已有研究基础上，通过体内外研究体系，探讨IL-27在银屑病中对Lag3+Treg的作用及调控机制，为探索银屑病治疗新靶点提供理论和实验依据。

银屑病是常见的慢性炎症性皮肤病，炎症性T细胞促进该病发生，而调节性T细胞(Treg) 下调炎症。Lag3是一种可介导Treg抗炎作用的跨膜蛋白，Lag3+Treg含量似与炎症负相关，但 调控机制未明。IL-27是具有广泛免疫调节作用的细胞因子，在炎症性肠病及自身免疫性脑脊 髓膜炎中能上调Treg上的Lag3表达而延缓疾病进展，但是否参与银屑病的发展尚未知晓。前期研究我们发现：银屑病患者外周血及皮损中IL-27及其受体表达下调；Lag3+Treg细胞数目减少; IL-27治疗后的银屑病模型小鼠银屑病样皮损明显减轻，脾脏中Lag3表达上调而FOXP3+Treg细胞总数未见明显增加，提示IL-27可能调控Treg细胞的功能而缓解银屑病的发展，但调控机制不详。通过本课题的研究我们发现：IL-27刺激后的银屑病患者PBMC中LAG3+Treg细胞明显上调，同时咪喹莫特诱导的IL-27基因敲除小鼠银屑病模型中银屑病样皮损明显加重，同时皮损中LAG3+Treg细胞的表达下调。离体实验也发现IL-27直接刺激Treg中LAG3的表达。以上的研究我们得出：IL-27在银屑病中通过调节Lag3+Treg细胞而发挥抗炎作用，为探索银屑病治疗新靶点提供理论和实验依据。