近来研究发现，自噬在免疫调节中发挥重要的作用，树突状细胞（DC）可通过自噬小体为MHCII类区室提供外源性抗原，促进其加工提呈，启动排斥反应。我们已申请专利的小分子环肽CHBP与自噬密切相关，它可通过激活Jak-2/STAT3/SOCS1通路，抑制DC的成熟，也可使DC自噬相关蛋白LC3II/I表达显著下降，并在肾损伤中调控mTOR介导的自噬，在大鼠肾移植模型中显著减轻排斥反应。因此我们推测：CHBP可能通过调控mTOR信号抑制DC自噬，降低其MHC II类分子及共刺激分子表达，抑制了DC提呈移植肾抗原的能力，从而减轻排斥反应。为此，本项目将利用DC激活的体外模型和DC特异性MHC II类分子敲除的小鼠肾移植模型，阐明CHBP抑制DC自噬的分子机制，并探索基于CHBP的细胞治疗。该项目将明晰DC自噬在移植肾排斥中的机理，解析CHBP的抗排斥机制，为CHBP临床转化提供理论基础和实验支持。

Dendritic cells (DC) play a key role in the initiation of rejection in kidney transplantation. Recently, it is reported that autophagosome provides external antigens for MHC II compartment to process and present. Cyclic helix B peptide (CHBP), as our patented drug, has been demonstrated to ameliorate renal allograft acute rejection and inhibit dendritic cells (DC) maturation via activation of Jak-2/STAT3/SOCS1. In our previous studies, CHBP decreased the LC3II/I expression of DC, and modulated mTOR-dependent autophagy in acute kidney injury. Hence, we hypothesize that CHBP inhibits DC autophagy, and then decreases the expression of MHC II and co-stimulator molecules by modulating mTOR signal. Then CHBP inhibits the antigen presenting ability and rejection. In this proposal, we will demonstrate the mechanism that CHBP inhibits DC autophagy using DC specific MHC II deficient mice and mice kidney transplantation model. The results will not only demonstrate the mechanism of anti-rejection by CHBP, but also promote the understanding of the interaction between DC autophagy and renal allograft rejection. It will be also benefit for CHBP translation in future.