供者致耐受树突状细胞（Tol-DCs）能够诱导肾脏移植耐受。新近报道胞浆中XBP1 mRNA的变化影响DCs的功能和机体的免疫状态，我们也发现DC前体细胞（pre-DCs）分化为Tol-DCs的过程与XBP1 mRNA的调控相关联。活化的IRE1可能通过剪切XBP1 mRNA后翻译的XBP1-S活化DCs，IRE1-RIDD通路对DCs功能的抑制也可能受到XBP1 mRNA反馈调节。由此设想：XBP1 mRNA的下调通过IRE1-XBP1和IRE1-RIDD双通路介导，诱导pre-DCs分化为Tol-DCs。我们将首先验证下调XBP1 mRNA对Tol-DCs的诱生效应，在此基础上分别阻断IRE1-XBP1和IRE1-RIDD双通路，通过体外功能检测和小鼠肾脏移植模型，对诱生Tol-DCs的致耐受能力进行再次评估，从而验证这一机理。本研究将为肾脏移植的细胞治疗和分子治疗提供新路径。

Donor-derived tolerogenic dendritic cells (Tol-DCs）are capable to induce tolerance in kidney transplantation. Accumulating findings show that XBP1 mRNA in the cytoplasma modulates the function of DCs and therefore the systemic immunological status. We have induced DC precursors (pre-DCs) differentiation into Tol-DCs which may be related with XBP1 mRNA intervention. After splicing XBP1 mRNA by active IRE1, XBP1-S is translated and then actives DCs, while the inhibition of DCs by IRE1-RIDD pathway may be modulated feedback by XBP1 mRNA. Herein, we hypothesize that the down-regulation of XBP1 mRNA can induce pre-DCs differentiation to Tol-DCs through both the IRE1-XBP1 and IRE1-RIDD pathways. In this proposal, to verify this hypothesis, we plan to induce Tol-DCs by down-regulating XBP1 mRNA firstly, then block IRE1-XBP1 and IRE1-RIDD pathwaysse parately, and re-evaluate the function of the induced Tol-DCs by ex-vivo examination and kidney transplantation in mice. This study provides novel strategies on cell therapy and molecular therapy for kidney transplantation.