Role of programmed death ligand 1 and Kupffer cell in immune regulation after orthotopic liver transplantation in rats
Role of programmed death ligand 1 and Kupffer cell in immune regulation after orthotopic liver transplantation in rats
复制标题
程序性死亡配体1和库普弗细胞在大鼠原位肝移植后免疫调节中的作用
DOI：
10.1016/j.intimp.2017.04.009
复制
发表时间：
2017-07-01
影响因子：
5.6
通讯作者：
Zeng, Zhong
中科院分区：
文献类型：
--
作者：
Gong, Junhua;Cao, Ding;Zeng, Zhong
前言：程序性死亡配体1(PD-L1)和枯否细胞(KCs)在肝移植免疫调节中的作用尚不清楚。方法：Lewis和Brown-挪威(BN)大鼠分为Lew-BN组(Lewis-to-BN肝移植)和BN-BN组(BN-to-BN组)。组织学、细胞因子和PD-L1产生的评估。H-3-胸腺嘧啶核苷(H-3-TdR)共培养法检测PD-L1和KCs对T细胞的影响。结果：BN-BN组受者存活时间较长，而LEW-BN组则出现急性排斥反应。ELISA法显示，移植后第7天，BN-BN组血浆IL-2、干扰素-γ、肿瘤坏死因子-α水平显著低于Lew-BN组，而IL-10水平显著高于Lew-BN组(P<0.05)。BN-BN组KCs PD-L1表达明显高于Lew-BN组(P<；0.05)。KCs+TCS组TCS增殖率明显低于TCS组，凋亡率显著高于TCS组(P<；0.05)。KCS+TCS组IL-2、TNF-α、INF-γ水平显著高于TCS组(P<0.05)，而IL-10水平低于TCS组(P<0.05)。转染组IL-2、干扰素-γ和肿瘤坏死因子-α水平显著高于未转染组，而IL-10水平显著低于未转染组(P<；0.05)。结论：PD-L1高表达的KCS可显著抑制TCS的增殖和功能。体内沉默KCs中PD-L1的表达可恢复TCS的功能。
Introduction: Role of programmed death ligand 1 (PD-L1) and Kupffer cells (KCs) in liver transplantation immune regulation was unclear.Methods: Lewis and Brown-Norway (BN) rats were assigned to LEW-BN group (Lewis-to-BN liver transplantation) and BN-BN group (BN-to-BN). Receipts were sacrificed for histology and assessment of cytokines and PD-L1 production. Effect of PD-L1 and KCs on T cells (TCs) was monitored by co-culture of H-3-Thymidine TCs. KCs transfected with PD-L1-shRNA interference plasmids were co-cultured with TCs, PD-L1 expression and cytokines production were measured respectively.Results: Recipients in BN-BN group survived a long time while acute rejection was found in LEW-BN group. ELISA showed plasma levels of IL-2, IFN-gamma and TNF-alpha in BN-BN group were significantly lower and levels of IL-10 were significantly higher than that in LEW-BN group on day 7 after transplantation (P < 0.05). PD-L1 expression of KCs in BN-BN group was significantly higher than that in the LEW-BN group (P < 0.05). Proliferation rate of TCs in KCs + TCs group was significantly lower and its apoptosis rate was significantly higher than that in TCs group (P < 0.05). IL-2, TNF-alpha and INF-gamma levels were remarkably higher and IL-10 levels were lower in KCs + TCs group than that in TCs group (P < 0.05). Levels of IL-2, IFN-gamma and TNF-alpha in transfection group were significantly higher and that of IL-10 was notably lower than that in the un-transfected group (P < 0.05).Conclusion: KCs with high expression of PD-L1 could significantly suppress the proliferation and function of TCs. Silencing the expression of PD-L1 in KCs in vivo could restore the function of TCs.