环肽CHBP抑制树突状细胞成熟在防治移植肾急性排斥反应中的机制

急性排斥反应是肾移植领域仍难以完全攻克的障碍。CHBP是我们已申请专利的小分子肽，目前处于专利公告阶段。我们发现，CHBP能显著减轻大鼠移植肾急性排斥反应，减少移植肾内成熟DC的浸润，且DC表达CHBP的受体TPR，该受体可启动Jak/STAT信号，经CHBP治疗的移植肾内Jak/STAT下游的SOCS1和SOCS3 基因表达显著上调，而SOCS可抑制Toll样受体的下游信号。因此，我们推测：CHBP通过TPR激活DC内Jak/STAT/SOCS通路，下调由Toll样受体启动的DC活化信号，抑制DC的成熟。为此，本项目拟利用成熟的大鼠肾移植模型，进一步明确CHBP抗移植肾急性排斥及对局部和外周DC成熟的抑制作用，并利用基因敲除等手段，阐明CHBP抑制DC成熟的机制，找寻关键SOCS靶蛋白，最终验证该蛋白在体内与CHBP抗排斥作用的相关性，为CHBP的临床转化提供理论基础和实验支持。

Acute rejection is one of major challenges in transplantation treatment. We have patented a small molecular peptide, cyclic helix B peptide (CHBP), which has renoprotective effects in a rat kidney transplantation model. In our previous study, CHBP reduced infiltration of mature dendritic cells (DC) in kidney allograft, suggesting that CHBP have an inhibitory effect on DC maturation. Interestingly DC expresses tissue protective receptor, the ligand to CHBP, which could be activated by Jak/STAT pathway. CHBP significantly increased mRNA expression of SOCS1 and SOCS3, a downstream signal in Jak/STAT pathway. Therefore it is proposed in the present study that CHBP may inhibit DC maturation through Jak/STAT/SOCS pathway. To this end, cell culture experiments will be performed for mechanism study. And a rat kidney transplantation model will be applied to support our in vitro results. The present study may represent a novel therapeutic target for the treatment of acute rejection.