CD205-TLR9-IL-12 axis contributes to CpG-induced oversensitive liver injury in HBsAg transgenic mice by promoting the interaction of NKT cells with Kupffer cells  

作　　者：Xin Hou Xiaolei Hao Meijuan Zheng Congfei Xu Jun Wang Rongbin Zhou Zhigang Tian 

机构地区：[1]Anhui Provincial Laboratory of Microbiology and Parasitology,Department of Microbiology and Parasitology,Anhui Medical University,Hefei 230032,China [2]Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Life Sciences and Medical Center,University of Science and Technology of China,Hefei 230027,China [3]Department of Clinical Laboratory,First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [4]Innovation Center for Cell Biology,Hefei National Laboratory for Physical Sciences at Microscale,Hefei 230027,China

出　　处：《Cellular & Molecular Immunology》2017年第8期675-684,共10页中国免疫学杂志（英文版）

基　　金：supported by the Natural Science Foundation of China(81571540,91429303,81361120388,31390433 and 81302525);the National Science&Technology Major Projects(2013ZX10002002-002);the open project of the CAS Key Laboratory of Innate Immunity and Chronic Disease(KLIICD-201509).

摘　　要：Gut-derived bacterial products contribute to liver inflammation and injury during chronic hepatitis B virus infection;however,the underlying mechanisms remain obscure.In this study,hepatitis B surface antigen transgenic(HBs-Tg)mice and their wild-type(WT)control C57BL/6 mice were injected with CpG-oligodeoxynucleotides(ODNs)to mimic the translocation of gut microbial products into the systemic circulation.We found that,compared with the WT mice,the HBs-Tg mice were oversensitive to CpG-ODN-induced liver injury,which was dependent on natural killer T(NKT)cells.CpG-ODN injection enhanced the expression of Fas ligand(FasL)on NKT cells.In addition,hepatocytes from the HBs-Tg mice expressed higher levels of Fas than did those from the WT mice,which was further augmented by CpG-ODN.Interaction of Fas and FasL was involved in the cytotoxicity of NKT cells against hepatocytes in the HBs-Tg mice.Moreover,Kupffer cells in the HBs-Tg mice expressed higher levels of CD205 and produced greater amounts of interleukin(IL)-12 than did those in the WT mice.Finally,the depletion of Kupffer cells,neutralization of IL-12 or specific silencing of CD205 on Kupffer cells significantly inhibited CpG-ODN-induced liver injury and NKT activation in the HBs-Tg mice.Our data suggest that CD205-expressing Kupffer cells respond to CpG-ODNs and subsequently release IL-12 to promote NKT cell activation.Activated NKT cells induce liver damage through the Fas signaling pathway in HBs-Tg mice.

关 键 词：CPG hepatitis B virus Kupffer cell liver injury NKT cell 

分 类 号：R73[医药卫生—肿瘤]