Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage.
Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage.
复制标题
DOI：
10.1084/jem.20061287
复制
发表时间：
2007-03-19
期刊：
影响因子：
--
通讯作者：
Maini MK
中科院分区：
文献类型：
--
作者：
Dunn C;Brunetto M;Reynolds G;Christophides T;Kennedy PT;Lampertico P;Das A;Lopes AR;Borrow P;Williams K;Humphreys E;Afford S;Adams DH;Bertoletti A;Maini MK
乙肝病毒在全球超过3.5亿人中造成慢性感染。它在肝细胞中复制，但不引起细胞病变；肝损伤被认为是由免疫介导的。在这里，我们研究了先天免疫反应在慢性乙肝患者肝损伤中的作用。纵向分析显示，肝脏炎症程度与IL-8、干扰素-α和自然杀伤细胞(NK细胞)肿瘤坏死因子相关的凋亡诱导配体(TRAIL)表达的波动之间存在时间相关性。一项横断面研究证实了与健康携带者相比，患有乙肝病毒相关性肝炎的患者的这些发现。慢性乙肝患者肝脏中活化的、表达TRAIL的NK细胞进一步丰富，而他们的肝细胞表达的TRAIL死亡诱导受体水平增加。患者体内的干扰素-α浓度能够激活NK细胞，在体外诱导TRAIL介导的肝细胞凋亡。干扰素-α/IL-8联合作用可使肝细胞上表达的TRAIL受体和死亡诱导受体的平衡失调，从而进一步增强该途径的致病潜能。我们得出结论，NK细胞可能通过TRAIL介导的肝细胞死亡而参与肝脏炎症，并证明这种非抗原特异性的机制可以通过活动性乙肝病毒感染过程中产生的细胞因子来启动。
Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-α, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-α concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-α/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection.
登录
查看更多内容
DOI：
10.1084/jem.189.2.441
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Afford SC;Randhawa S;Eliopoulos AG;Hubscher SG;Young LS;Adams DH
通讯作者：
Adams DH
影响因子：
4.4
作者：
Campbell, JJ;Qin, SX;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
25.7
作者：
Brunetto, MR;Oliveri, F;Bonino, F
通讯作者：
Bonino, F
DOI：
10.1084/jem.186.7.1077
发表时间：
1997-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khabar KS;Al-Zoghaibi F;Al-Ahdal MN;Murayama T;Dhalla M;Mukaida N;Taha M;Al-Sedairy ST;Siddiqui Y;Kessie G;Matsushima K
通讯作者：
Matsushima K
影响因子：
4.4
作者：
Kafrouni, MI;Brown, GR;Thiele, DL
通讯作者：
Thiele, DL