Human TIGIT on porcine aortic endothelial cells suppresses xenogeneic macrophage-mediated cytotoxicity
Human TIGIT on porcine aortic endothelial cells suppresses xenogeneic macrophage-mediated cytotoxicity
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DOI：
10.1016/j.imbio.2019.07.008
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发表时间：
2019-09-01
期刊：
影响因子：
2.8
通讯作者：
Miyagawa, Shuji
中科院分区：
文献类型：
--
作者：
Noguchi, Yuki;Maeda, Akira;Miyagawa, Shuji
目的：由强的细胞介导的先天性和适应性异种免疫反应引起的延迟性排斥反应仍然是主要障碍，因此，抑制巨噬细胞功能可以有效地避免这种类型的排斥反应。材料与方法：将猪主动脉内皮细胞（PAEC）和TIGIT转染的PAEC（PAEC/ TIGIT）与M1巨噬细胞共培养，用磁珠计数法检测PAEC对M1巨噬细胞的细胞毒性。结果：M1和M2巨噬细胞均表达CD 155，而TIGIT在M2巨噬细胞中高表达，而在M1巨噬细胞中不表达。PAEC上的TIGIT显著降低M1巨噬细胞的细胞毒性，但未检测到对吞噬作用的显著抑制。TIGIT还引起Ml巨噬细胞中促炎细胞因子（即TNF α、IL-1 β和IL-12）的表达降低。此外，PAEC/TIGIT引起了显着增加磷酸化SHP-1在M1巨噬细胞相比PAEC.Conclusion：这项研究的结果表明，TIGIT抑制异种M1巨噬细胞诱导的细胞毒性，可能至少部分，通过磷酸化SHP-1。此外，在与PAEC/TIGIT一起培养的Ml巨噬细胞中观察到一些促炎细胞因子（即TNF α、IL-1 β和IL-12）的表达减少。
Purpose: The delayed rejection caused by strong cell-mediated innate and adaptive xenogeneic immune responses continues to be a major obstacle.Therefore, suppressing macrophage function could be effective in avoiding this type of rejection. In this study, the suppression of T-cell immunoglobulin and ITIM domain (TIGIT) function against macrophage-mediated xenogeneic rejection was investigated.Material and methods: Naive porcine aortic endothelial cell (PAEC) and PAEC transfectant with TIGIT (PAEC/ TIGIT) were co-cultured with Ml macrophages, and the degree of cytotoxicity was determined by a counting beads assay. The anti/pro-inflammatory gene expression was determined by RT-PCR and the phosphorylated SHP-1 in the macrophages after co-culturing with PAEC or PAEC/TIGIT was evaluated by western blotting.Results: CD155 was expressed at essentially equal levels on both M1 and M2 macrophages, whereas TIGIT was highly expressed on M2 macrophages but not in M1 macrophages. TIGIT on PAEC significantly reduced the cytotoxicity of M1 macrophages but no significant suppression of phagocytosis was detected. TIGIT also caused a decrease in the expression of pro-inflammatory cytokines, namely TNF alpha, IL-1 beta and IL-12 in Ml macrophages. Furthermore, PAEC/TIGIT caused a significant increase in phosphorylated SHP-1 in M1 macrophages compared to PAEC.Conclusion: The findings of this study indicate that TIGIT suppresses xenogeneic M1 macrophage-induced cytotoxicity, probably at least in part, via the phosphorylation of SHP-1. In addition, the reduced expression of some pro-inflammatory cytokines, namely TNF alpha, IL-1 beta and IL-12, was observed in Ml macrophages that had been cultured with PAEC/TIGIT.