Imbalance of interleukin-17-producing CD4 T cells/regulatory T cells axis occurs in remission stage of patients with hepatitis B virus-related acute-on-chronic liver failure
Imbalance of interleukin-17-producing CD4 T cells/regulatory T cells axis occurs in remission stage of patients with hepatitis B virus-related acute-on-chronic liver failure
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乙型肝炎病毒相关慢加急性肝衰竭患者缓解期产生白细胞介素17的CD4 T细胞/调节性T细胞轴失衡
DOI：
10.1111/jgh.12082
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发表时间：
2013-03-01
影响因子：
4.1
通讯作者：
Gao, Zhi-Liang
中科院分区：
文献类型：
--
作者：
Zhang, Geng-Lin;Xie, Dong-Ying;Gao, Zhi-Liang
背景与目的：虽然调节性T细胞（Treg）和产生白细胞介素17的CD4 T细胞（Th17）已被证明在炎症相关疾病中发挥相反的作用，但它们在乙型肝炎病毒（HBV）相关慢加急性肝衰竭（ACLF）不同阶段的频率和平衡仍不清楚。方法：对14例HBV相关ACLF患者进行研究，并根据疾病活动度将其划分为不同阶段。通过流式细胞术分析循环 Th17 细胞和 Treg 细胞，通过酶联免疫吸附测定对细胞因子进行定量。结果与病毒载量的时间变化、疾病进展相关，并与 30 名慢性乙型肝炎 (CHB) 受试者和 18 名健康受试者进行比较。结果：我们发现，与进展期、CHB 组或正常对照相比，ACLF 缓解期循环 Th17 细胞的频率显着更高。然而，与进展期或 CHB 组相比，ACLF 缓解期循环 Treg 细胞的频率明显较低。 Th17细胞的增加和随之而来的Treg细胞的减少造成了ACLF患者缓解期的不平衡，这与疾病进展呈负相关。此外，我们发现缓解期的 ACLF 患者调节 Th17 细胞和 Treg 细胞诱导的细胞因子谱发生改变。结论：缓解期的 ACLF 患者存在 Th17 与 Treg 细胞的不平衡，这可以作为预测疾病进展的预后标志物。这种不平衡可能在 HBV 相关 ACLF 的免疫发病机制中发挥作用。
Background and Aim: Although regulatory T cells (Treg) and interleukin-17-producing CD4 T cells (Th17) have been demonstrated to play opposing roles in inflammation-associated diseases, their frequency and balance in different stages of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remain unknown.Methods: Fourteen patients with HBV-associated ACLF were studied and defined into different stages according to disease activity. Circulating Th17 cells and Treg cells were analyzed by flow cytometry, and the cytokines were quantitated by enzyme-linked immunosorbent assay.Results were correlated with temporal changes in viral load, disease progression and compared with 30 chronic hepatitis B (CHB) subjects and 18 healthy subjects. Results: We showed a significantly higher frequency of circulating Th17 cells in the remission stage of ACLF when compared with the progression stage, the CHB group, or normal controls. However, the frequency of circulating Treg cells was significantly lower in the remission stage of ACLF when compared with the progression stage or the CHB group. The increase in Th17 cells and concomitant decrease in Treg cells created an imbalance in the remission stage of ACLF patients, which negatively correlated with disease progression. In addition, we showed that ACLF patients in the remission stage had an altered profile of cytokines that regulated the induction of Th17 cells and Treg cells.Conclusions: ACLF patients in the remission stage had an imbalance of Th17 to Treg cells, which could be used as a prognostic marker to predict disease progression. This imbalance could play a role in the immunopathogenesis of HBV-related ACLF.