Notch Signaling Regulates Circulating T Helper 22 Cells in Patients with Chronic Hepatitis C
Notch Signaling Regulates Circulating T Helper 22 Cells in Patients with Chronic Hepatitis C
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DOI：
10.1089/vim.2017.0007
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发表时间：
2017-09-01
期刊：
影响因子：
2.2
通讯作者：
Zhu, Guang-Ze
中科院分区：
文献类型：
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作者：
Jiang, Ben-Chun;Liu, Xin;Zhu, Guang-Ze
Notch信号增强了产生白细胞介素(IL)-22的CD4(+) T细胞（被定义为T辅助22 （Th22）细胞）和Notch-芳烃受体(AhR)-IL-22轴微调炎症反应的反应。以往的研究表明，Notch信号和Th22细胞都参与了慢性丙型肝炎病毒（HCV）感染的发病机制。因此，在本研究中，我们旨在研究Notch信号在Th22细胞中对HCV感染的调节作用。共有59例慢性丙型肝炎患者和22例正常对照（nc）参加了这项研究。分析γ -分泌酶抑制剂对Th22细胞百分比及相关转录因子和细胞因子mRNA表达的影响。慢性丙型肝炎患者Th22细胞频率明显高于非传染性肝炎患者。Notch信号的抑制下调了hcv特异性Th22细胞和IL-22的产生，这伴随着AhR和调节细胞因子（IL-6和肿瘤坏死因子- α）的减少。此外，Notch信号的抑制也降低了正常和hcv感染的HepG2细胞/Huh7.5细胞中il -22介导的抗菌反应。这一过程还伴随着信号转导和转录3信号激活因子的抑制。综上所述，目前的研究结果表明Notch信号通路在慢性丙型肝炎患者对IL-22的应答中起着关键作用，因此Notch- th22轴可能被认为是hcv感染患者的一个新的治疗靶点。
Notch signaling enhanced the response of interleukin (IL)-22-producing CD4(+) T cells that were defined as T helper 22 (Th22) cells, and Notch-aryl hydrocarbon receptor (AhR)-IL-22 axis fine-tuned inflammatory response. Previous studies have demonstrated that both Notch signaling and Th22 cells took part in the pathogenesis of chronic hepatitis C virus (HCV) infection. Thus, in this study, we aimed at examining the regulatory role of Notch signaling in Th22 cells in HCV infection. A total of 59 patients with chronic hepatitis C and 22 normal controls (NCs) were enrolled in this study. The percentage of Th22 cells and mRNA expression of related transcriptional factors and cytokines were analyzed in response to gamma-secretase inhibitor. Th22 cell frequency was significantly elevated in chronic hepatitis C in comparison with that in NCs. Inhibition of Notch signaling downregulated HCV-specific Th22 cells and IL-22 production, which was accompanied by the reduction of AhR and modulatory cytokines (IL-6 and tumor necrosis factor-alpha). Moreover, the suppression of Notch signaling also decreased the IL-22-mediated antimicrobial response in both normal and HCV-infected HepG2 cells/Huh7.5 cells. This process was also accompanied by the depression of signal transducers and activators of transcription 3 signaling. In conclusion, the current results suggested that Notch signaling acted as a critical pathway in determining the response to IL-22 in chronic hepatitis C. Thus, Notch-Th22 axis might be considered a new therapeutic target for HCV-infected patients.