Expression data from graft infiltrating macrophages treated with mTORi-HDL nanobiologics

Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Recent data demonstrate that non-self recognition by graft infiltrating macrophages initiates transplant rejection. Using an experimental transplantation mouse model, we isolated graft-infiltrating macrophages from two transplantation settings: untreated rejecting mice and treated with mTORi-HDL nanobiologics. We used microarrays to detail the global programme of gene expression underlying macrophage dependent organ transplant rejection and identified distinct classes of up-regulated genes during this process, which are down-regulated following tolerogenic treatment with mTORi-HDL nanobiologics. BALB/c donor hearts were transplanted into fully allogeneic C57BL/6 mice. Transplant recipients were either left untreated (Control) and rejected their allografts or were treated with mTORi-HDL nanobiologics (Sample) on days 0, 2, and 5 post-transplantation. Donor heart allografts were isolated on day 6 post-transplantation and graft-infiltrating macrophages were isolated by fluorescence-activated cell sorting (FACS) for microarray analysis.

无需长期免疫抑制即可诱导移植物耐受，仍是器官移植领域尚未攻克的核心难题。近期研究数据显示，移植物浸润巨噬细胞（graft infiltrating macrophages）对非己成分的识别可启动移植排斥反应。本研究依托实验性移植小鼠模型，从两种移植处理条件下分离得到移植物浸润巨噬细胞：未接受治疗的排斥反应小鼠，以及经mTORi-HDL纳米生物制剂处理的小鼠。我们通过基因芯片（microarrays）详细解析了巨噬细胞依赖型器官移植排斥反应背后的全局基因表达程序，并鉴定出该过程中上调的不同基因类别，这些基因在经mTORi-HDL纳米生物制剂实施耐受诱导治疗后表达水平显著下调。本实验将BALB/c系供体心脏移植至完全同种异型的C57BL/6小鼠体内，移植受体小鼠分为两组：未接受任何治疗的对照组（Control），其异体移植物会发生排斥反应；以及在移植后第0、2、5天接受mTORi-HDL纳米生物制剂处理的样本组（Sample），于移植后第6天分离供体心脏异体移植物，并通过荧光激活细胞分选术（fluorescence-activated cell sorting, FACS）分离移植物浸润巨噬细胞，用于基因芯片分析。