The purpose of this study was to study the effect of inhibiting NLRC5 expression and function on CD4 + T cells, and islet and skin transplantation in mice. A murine skin graft model and islet cell transplantation model were established, and the expression of NLRC5 was compared in rejection and immune tolerance groups. Mice spleen-derived CD4 + T cells were cultured, purified, and enriched in vitro, and transfected with the shRNA lentiviral vector NLRC5-RNAi-GFP. Changes in cytokine secretion were detected to understand changes in immunological function. Murine islet and skin transplantation models were injected with CD4 + T cells transfected with the lentivirus, and the survival time of the grafts and the levels of IFN-γ and IL-10 were compared between groups. The expression of NLRC5 mRNA in islet and skin grafts was significantly increased. In vitro experiments showed that the expression of IL-4 and IL-10 was up-regulated in CD4 + T cells, and T cells differentiation turned to Th2 after inhibition of NLRC5. In vivo experiments showed that inhibition of NLRC5 prolonged islet and skin graft survival. Pathological examination showed that the rejection of transplanted skin and islets in the NLRC5-RNAi group was mild, and there was a correlation between high expression of NLRC5 and rejection of mouse islet and skin grafts. In summary, inhibition of NLRC5 can prolong islet and skin graft survival induce transplant immune tolerance through induction of the secretion of Th2 cytokines by CD4 + T cells.

本研究的目的是研究抑制NLRC5表达和功能对小鼠CD4+T细胞、胰岛和皮肤移植的影响。建立小鼠皮肤移植模型和胰岛细胞移植模型，比较排斥组和免疫耐受组NLRC5的表达情况。小鼠脾源性CD4+T细胞体外培养、纯化和富集，并用 shRNA 慢病毒载体 NLRC5-RNAi-GFP 转染。检测细胞因子分泌的变化以了解免疫功能的变化。小鼠胰岛和皮肤移植模型注射慢病毒转染的CD4+T细胞，比较移植物存活时间和IFN-γ、IL-10水平。NLRC5 mRNA在胰岛和皮肤移植物中的表达显着增加。体外实验表明，IL-4和IL-10在CD4+T细胞中表达上调，NLRC5抑制后T细胞分化转为Th2。体内实验表明，NLRC5 的抑制延长了胰岛和皮肤移植物的存活。病理检查显示NLRC5-RNAi组移植皮肤和胰岛的排斥反应较轻，NLRC5高表达与小鼠胰岛和植皮排斥反应存在相关性。总之，抑制 NLRC5 可以延长胰岛和皮肤移植物的存活，通过诱导 CD4 + T 细胞分泌 Th2 细胞因子来诱导移植免疫耐受。