Tim-3 alters the balance of IL-12/IL-23 and drives TH17 cells: role in hepatitis B vaccine failure during hepatitis C infection.
Tim-3 alters the balance of IL-12/IL-23 and drives TH17 cells: role in hepatitis B vaccine failure during hepatitis C infection.
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DOI：
10.1016/j.vaccine.2013.03.003
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发表时间：
2013-04-26
期刊：
影响因子：
5.5
通讯作者：
Yao ZQ
中科院分区：
文献类型：
--
作者：
Wang JM;Ma CJ;Li GY;Wu XY;Thayer P;Greer P;Smith AM;High KP;Moorman JP;Yao ZQ
考虑到丙型肝炎病毒(丙型肝炎病毒)感染的共同危险因素以及重叠感染时与肝脏相关的发病率和死亡率增加，建议对丙型肝炎病毒(丙型肝炎病毒)感染者接种乙肝疫苗。在这种情况下，疫苗反应通常是迟钝的，与健康受试者相比，慢性丙型肝炎感染者对乙肝疫苗的应答率较低。在这项研究中，我们研究了T细胞免疫球蛋白粘蛋白结构域-3(Tim-3)介导的免疫调节在丙型肝炎病毒感染过程中乙肝疫苗应答中的作用。我们发现，T细胞耗竭的标志物Tim-3在单核细胞上过度表达，导致与丙型肝炎病毒感染的乙肝疫苗应答者或健康受试者(HS)相比，丙型肝炎病毒感染的乙肝疫苗无效者对IL-12/IL-23产生的调节不同，进而导致TH17细胞聚集。重要的是，体外阻断TIM-3信号，纠正了在丙型肝炎病毒感染期间观察到的乙肝疫苗无应答者IL-12/IL-23的失衡以及IL-17的偏向。这些结果表明，Tim-3介导的先天获得性免疫反应的失调参与了慢性丙型肝炎患者乙肝疫苗失败的原因，这增加了在慢性病毒感染的情况下阻断这一负信号通路可能提高乙肝免疫成功率的可能性。
Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production with in turn TH17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection.
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影响因子：
3.7
作者：
Gasse P;Riteau N;Vacher R;Michel ML;Fautrel A;di Padova F;Fick L;Charron S;Lagente V;Eberl G;Le Bert M;Quesniaux VF;Huaux F;Leite-de-Moraes M;Ryffel B;Couillin I
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Couillin I
影响因子：
20.3
作者：
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通讯作者：
Kapsenberg, ML
影响因子：
14.2
作者：
Louten, Jennifer;Boniface, Katia;Malefyt, Rene de Waal
通讯作者：
Malefyt, Rene de Waal
影响因子：
3.1
作者：
Kramer, Erik Seth;Hofmann, Charlotte;Sterling, Richard K.
通讯作者：
Sterling, Richard K.
影响因子：
50.3
作者：
Kortylewski M;Xin H;Kujawski M;Lee H;Liu Y;Harris T;Drake C;Pardoll D;Yu H
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Yu H