Implication of Th17 and Th1 Cells in Patients with Chronic Active Hepatitis B

Ge, Jian; Wang, Kai; Meng, Qingying; Zhang, Qi; Meng, Fanli; Fan, Yu–Chen

doi:10.1007/s10875-009-9328-2

Cited by 111 publications

(109 citation statements)

References 31 publications

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“…pp , 0.05 versus IgG control; ppp , 0.01 versus IgG control; # p , 0.05 between marked conditions. functions in response to TLR7 stimulation by viral ssRNA might play roles in the immune activation related to viral immune responses, in particular, because it was recently shown that the number of peripheral Th17 cells increased during chronic virus infections (48,49). Moreover, the data presented herein might be of relevance during the treatment of neoplastic skin lesions with R837, because it was shown that increasing numbers of PDCs infiltrate the treated skin area (10).…”

Section: Discussionmentioning

confidence: 69%

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Peng

Oldenburg

et al. 2009

The Journal of Immunology

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Signals involved in the commitment of Th17 differentiation are of substantial interest for our understanding of antimicrobial defense mechanisms and autoimmune disorders. Various ways in which myeloid dendritic cells modulate Th17 differentiation have been identified. However, although plasmacytoid dendritic cells (PDCs) are regarded as important players in antiviral/antimicrobial host defense and autoimmune diseases, a putative modulatory role of PDCs in Th17 differentiation has not yet been elucidated in detail. We demonstrated that PDCs are capable of promoting Th17 differentiation in response to TLR7 stimulation. Further, both the differentiation of Th17 cells from naive T cells and the amplification of Th17 effector functions of memory T cells are promoted by PDCs after TLR7 activation. Our data are of strong clinical relevance because TLR7 activation in PDCs might represent one of the missing links between innate and adaptive immune mechanisms and contribute to the amplification of Th17-driven autoimmune disorders as well as viral host defense.

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Section: Discussionmentioning

confidence: 69%

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Peng

Oldenburg

et al. 2009

The Journal of Immunology

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“…Besides, the compartmentalization of the IFN-γ from peripheral into liver might partly accounts for reduced peripheral IFN-γ level in ACHBLF patients. In addition, our previous study showed that the frequency of Th17 cells had a negative correlation with Th1 cells, and the imbalance of Th17 and Th1 cells may result in pathogenesis of CHB patients (Ge et al 2010). A considerably lower level of serum IFN-γ combined with a considerably higher level of intrahepatic IFN-γ could be a characteristic of ACHBLF (Ohta et al 2000).…”

Section: Discussionmentioning

confidence: 93%

Enhanced Demethylation of Interferon-.GAMMA. Gene Promoter in Peripheral Blood Mononuclear Cells Is Associated with Acute-on-Chronic Hepatitis B Liver Failure

Fan

Zou

Long

et al. 2011

Tohoku J. Exp. Med.

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Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to liver failure occurring in patients with chronic hepatitis B (CHB) related liver diseases. Interferon-γ (IFN-γ) plays an important role in the exacerbation of liver function. However, the exact mechanism, by which IFN-γ mediates ACHBLF, is not fully understood. Forty patients with ACHBLF, fifteen patients with CHB and ten healthy controls were included in this present study. ELISA was performed to measure the level of serum IFN-γ. The methylation status of IFN-γ promoter in peripheral blood mononuclear cells (PBMCs) was determined using methylation-specific PCR. Model for End-stage Liver Disease (MELD) scoring was performed for evaluating the severity of liver failure. The serum level of IFN-γ in patients with ACHBLF or CHB was significantly lower than that in healthy controls, while the serum IFN-γ level in ACHBLF patients was significantly higher than that in CHB patients. In ACHBLF patients, the level of IFN-γ was positively correlated with total bilirubin and MELD score, but negatively correlated with prothrombin time activity. These results suggest the involvement of IFN-γ in the pathogenesis of ACHBLF. Importantly, the degree of methylation of the IFN-γ gene promoter in ACHBLF patients (60%, 24/40) was significantly lower than that in CHB patients (93%, 14/15), but was higher than that in the control group (20%, 2/10). Furthermore, in ACHBLF patients, the serum IFN-γ level was significantly higher in unmethylation group than that in methylation group. In conclusion, enhanced demethylation of IFN-γ gene promoter in PBMCs may be associated with the onset of ACHBLF.

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“…However, IL-23 expression and its role in CHB are still unknown. Recent studies have demonstrated that Th17 cells increase the severity of liver damage in CHB patients (23)(24)(25), indicating that IL-23 may play an important role in promoting inflammatory injury in CHB. In the current study, we found that serum levels and hepatic IL-23 expression were positively corre-FIGURE 7.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have found that Th17 cells, which are expanded by IL-23, increase the severity of liver damage in patients with HBV (23)(24)(25), indicating that IL-23 may play an important role in promoting inflammatory injury in chronic hepatitis B (CHB). In this study, we evaluated the serum levels and hepatic expression of IL-23 in CHB patients and analyzed its correlation with HBVmediated inflammatory damage.…”

Section: H Epatitis B Virus (Hbv) Infection Is One Of the Leadingmentioning

confidence: 99%

Upregulation of IL-23 Expression in Patients with Chronic Hepatitis B Is Mediated by the HBx/ERK/NF-κB Pathway

Xia

Tian

Huang

et al. 2012

The Journal of Immunology

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IL-23 is a newly discovered proinflammatory cytokine that contributes to the maintenance and expansion of Th17 cells. IL-23 has recently been identified as playing a critical role in a number of chronic inflammatory diseases. However, the regulatory mechanism of IL-23 in chronic hepatitis B (CHB) remains largely unknown. The aims of this study were to detect the expression of IL-23 in CHB patients and to explore the molecular mechanism of hepatitis B virus (HBV)-induced IL-23 expression. Serum levels and hepatic expression of IL-23 were significantly upregulated in CHB patients. A positive correlation was found between IL-23 expression and the histological activity index score, HBV DNA load, and serum alanine aminotransferase and aspartate aminotransferase levels. HBx protein increased IL-23 expression in a dose-dependent manner. It also aided in the nuclear translocation of NF-κB, which directly bound to the promoters of IL-23 subunits p19 and p40 to facilitate their transcription. NF-κB inhibitors blocked the effect of HBx on IL-23 induction, and NF-κB subunits p65 and p50 increased the augmented IL-23 expression. Inhibition of ERK1/2 activation and transfection with ERK dominant-negative plasmid significantly blocked the HBx-induced IL-23 expression. Furthermore, PI3K and Ras–MEK–MAPK inhibitors significantly decreased the ERK1/2 activation and IL-23 expression. Thus, we report a new molecular mechanism for HBV-induced IL-23 expression, which involves the activation of the ERK/NF-κB pathway by HBx, leading to the transactivation of the IL-23 p19 and p40 promoters.

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Implication of Th17 and Th1 Cells in Patients with Chronic Active Hepatitis B

Abstract: The elevated peripheral Th17 cells were obtained in the patient with chronic active hepatitis B, suggesting its potential role in the immune activation of chronic HBV infection.

Cited by 111 publications

References 31 publications

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Enhanced Demethylation of Interferon-.GAMMA. Gene Promoter in Peripheral Blood Mononuclear Cells Is Associated with Acute-on-Chronic Hepatitis B Liver Failure

Upregulation of IL-23 Expression in Patients with Chronic Hepatitis B Is Mediated by the HBx/ERK/NF-κB Pathway

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