IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization
IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization
复制标题
IL-34 通过诱导库普弗细胞 M2 极化抑制大鼠肝移植的急性排斥反应
DOI:
10.1097/tp.0000000000002194
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发表时间:
2018-06-01
期刊:
影响因子:
6.2
通讯作者:
Wu, Zhongjun
中科院分区:
文献类型:
--
作者:
Zhao, Zhengfei;Pan, Guangrui;Wu, Zhongjun
Background. Recent studies have demonstrated that IL-34 is implicated in the regulation of macrophage functions. However, the effect of IL-34 on Kupffer cells (KCs) in acute rejection (AR) of liver transplantation remains unclear. Methods. IL-34 expression was detected in graft and serum from allotransplantation and syngeneic transplantation groups. The adeno- associated virus-expressing IL-34 was used to assess the effect of IL-34 on AR of rat liver transplantation. The effect of IL-34 on KC polarization was evaluated by in vitro and in vivo assays. Kupffer cells in donors were depleted by clodronate treatment before transplantation, and the nontreated KCs or lipopolysaccharide-treated KCs were transferred into recipients during liver transplantation. Results. IL-34 expression levels in grafts and serum were decreased in the allotransplantation group compared with the syngeneic transplantation group. Adeno-associated virus-expressing IL-34 treatment induced KC M2 polarization in vivo and inhibited the AR of rat liver transplantation. Moreover, we found that IL-34 switched the phenotype of KCs from M1 to M2 by activating the PI3K/Akt pathway in vitro. In addition, the results of KC deletion and adaptive transfer experiments showed that the AR inhibition induced by IL-34 was M2 KC-dependent. Conclusions. IL-34 plays an important role in KC M2 polarization-dependent AR inhibition of rat liver transplantation.