白细胞介素-35（IL-35）抑制角膜移植排斥反应的机制和信号通路研究

Immune rejection is the primary cause leading to the failure of corneal grafts. It has been proven lately that IL-35 can intensively inhibit the production of the effective T cells as well as increase the number of Treg, bringing the prospect of IL-35 treating autoimmune diseases in the spotlight. However, no studies have been reported in which IL-35 is put into preventing and treating the immunological rejection after organ transplantation. In this project, it's for the first time that the inhibitive effect of IL-35 on corneal grafting rejection and the intrinsic mechanism is enquired into with the use of corneal grafting model. Through structuring the expression vectors of IL-35 gene and transfecting the vectors into corneal grafts, observe the effect of the expressive level of IL-35 on the survival incidence of corneal grafts. Through testing the species and the emergying order of the immune cells in corneal grafts and lymphonodi cervicales and the expressive level of TGF-β、IL-10、IFN-γ、IL-12, probe into the mechanism of IL-35 inhibiting corneal grafting rejection. Through observing the effects of IL-35 on IL-35 receptors on the surface of DCs and JAK,STAT inside DCs, enquire into the signal-transmission pathways playing roles in the tolerance-inducing effect of IL-35 on DCs. This study is aimed at finding a brand new target to intervene with for the prevention and treatment of corneal grafting rejection, and also providing a different approach of developing new specific immunosuppressive drugs.

免疫排斥反应是导致角膜移植失败的最主要原因。最新研究发现，白细胞介素35（IL-35）具有强力抑制效应性T细胞的产生，扩增调节性T细胞数量的作用，用于自身免疫性疾病的治疗前景引人瞩目。然而，应用IL-35预防和治疗移植排斥反应未见报道。本课题首次利用角膜移植模型，探讨IL-35对角膜移植排斥的抑制作用及其机制。通过构建IL-35基因表达载体并转染到小鼠角膜植片上，观察其表达水平对术后植片存活的影响；通过检测植片和颈部淋巴结中免疫细胞的种类和出现顺序及细胞因子TGF-β、IL-10等表达，探讨IL-35抑制角膜移植排斥的机制；通过观察IL-35对树突状细胞（DCs）表面IL-35受体及DCs细胞JAK和STAT 激酶活性的影响，探讨IL-35诱导DCs细胞耐受的信号通路。此研究旨在为预防和治疗角膜移植排斥找到新的干预靶点，为开发新的特异性免疫抑制药物提供新的途径。

免疫排斥反应是导致角膜移植失败的最主要原因。最新研究发现，白细胞介素35（IL-35）具有强力抑制效应性T细胞的产生，扩增调节性T细胞数量的作用，用于自身免疫性疾病的治疗前景引人瞩目。然而，应用IL-35预防和治疗移植排斥反应未见报道。本课题首次利用角膜移植模型，探讨IL-35对角膜移植排斥的抑制作用及其机制。通过构建IL-35基因表达载体并转染到小鼠角膜植片上，观察其表达水平对术后植片存活的影响；通过检测植片和颈部淋巴结中免疫细胞的种类和出现顺序及细胞因子TGF-β、IL-10等表达，探讨IL-35抑制角膜移植排斥的机制；通过观察IL-35对树突状细胞（DCs）表面IL-35受体及DCs细胞JAK和STAT 激酶活性的影响，探讨IL-35诱导DCs细胞耐受的信号通路。此研究旨在为预防和治疗角膜移植排斥找到新的干预靶点，为开发新的特异性免疫抑制药物提供新的途径