Decreased frequency of circulating Th9 cells in patients with chronic hepatitis B infection

Cui, Meilan; Lv, Ying; Lu, Jianhua; Zhang, Wei; Duan, Yuanyuan; Huang, Yan; Yang, Lei; Li, Man; Liu, Wenxuan; Liu, Dianwu; Yan, Huimin

doi:10.1002/jcla.22246

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…Th9 and Tc9-secreting IL-9 still strongly inhibited coxsackie virus B3 replication without induction of apoptosis in cardiomyocytes ( 24 ), although the viral myocarditis did not mainly contribute to differentiation and proliferation of Th9 cells ( 25 ). In line with previous report ( 9 ), our current results suggested a decreased serum IL-9 and circulating non-specific and HBV-specific Th9 cells, but not Tc9 cells, in CHB and hepatitis B-related HCC. This indicated that decreased Th9 cells might mainly account for down-regulation of IL-9 during chronic HBV infection.…”

Section: Discussionsupporting

confidence: 93%

“…IL-9-producing T cells and IL-9 secretion contributes to tumor immunity and immune-related diseases, which provides useful insight into pathogenesis and treatment ( 7 , 8 ). Cui et al revealed that circulating Th9 cells was notably lower in chronic hepatitis B (CHB) patients, and no significant differences in Tc9 percentage between CHB patients and controls ( 9 ). However, the profile of viral specific Th9 and Tc9 cells and regulation of IL-9 secretion in HBV-related HCC was not reported.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-35 Suppresses Interleukin-9-Secreting CD4+ T Cell Activity in Patients With Hepatitis B-Related Hepatocellular Carcinoma

et al. 2021

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Chronic hepatitis B virus (HBV) infection induces dysfunction of immune response and chronic liver damage. However, the mechanisms that account for HBV-related hepatocellular carcinoma (HCC) are poorly understood. The aim of present study was to investigate the modulatory role of interleukin (IL)-35, an immunosuppressive cytokine, to IL-9-secreting T cells in hepatitis B-related HCC. Twenty-two HBV-related HCC patients, twenty-seven chronic hepatitis B (CHB) patients, and eleven controls were enrolled. Serum IL-35 and IL-9 concentration was measured by ELISA. Peripheral and liver-infiltrating non-specific and HBV-specific Th9 and Tc9 cells were assessed by flow cytometry. The regulatory activity of IL-35 to peripheral and liver-infiltrating Th9 cells was assessed in co-culture system between CD8+ T cells and HepG2.2.15 cells. Serum IL-35 was up-regulated, while IL-9 was down-regulated in HBV-related HCC patients compared with in CHB patients and controls. Peripheral non-specific and HBV-specific Th9 cells, but not Tc9 cells, were decreased in HBV-related HCC patients. Liver-infiltrating non-specific and HBV-specific Th9 cells were also reduced in HCC tumor sites. CD8+ T cells from CHB and HBV-related HCC patients revealed decreased cytotoxicity compared with those from controls. Autologous Th9 cells mediated the elevation of CD8+ T cell cytotoxicity, and this process was depending on IL-9 secretion. Recombinant IL-35 stimulation inhibited IL-9 secretion and PU.1 mRNA expression in non-specific and HBV-specific Th9 cells, leading to the suppression of Th9-mediated CD8+ T cell cytotoxicity in CHB and HBV-related HCC patients. Our current data indicated that IL-35 might dampen non-specific and HBV-specific Th9 cells activity in HBV-related HCC patients.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Interleukin-35 Suppresses Interleukin-9-Secreting CD4+ T Cell Activity in Patients With Hepatitis B-Related Hepatocellular Carcinoma

et al. 2021

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“…By contrast, another group of investigators reported there was no significant difference in the percentage of Th9 cells, serum IL9 and IL10 levels among different groups (CHB and CHB-LC), no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients, and no obvious correlation between the percentage of Th9 cells, levels of IL9, and IL10 with age, total bilirubin, albumin, ALT, and HBV DNA levels [ 44 ]. Similarly, Cui, et al [ 45 ] showed that the frequency of circulating Th9 cells was significantly lower in chronic HBV patients than controls, and the percentages of Th9 cells were negatively correlated with HBV DNA loads. The discrepancies might be explained, at least in part, to the difference in levels of HBV DNA load and the difference in study populations.…”

Section: Discussionmentioning

confidence: 93%

Role of T-Helper 9 Cells in Chronic Hepatitis C-Infected Patients

Ali

El‐Badawy

Afifi

et al. 2018

Viruses

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Hepatitis C virus is a hepatotropic virus that is transmitted parenterally. Viral infections are usually associated with modulations of the immune cells, leading to enhanced viral survival and spreading, and accordingly, life-threatening complications. Recently, it has been proposed that a new subset of T-helper, named T-helper 9, is involved in the pathogenesis of different immunopathological conditions, such as allergies, tumors, and viral infections. Some studies reported a protective role, and others described a pathogenic potential for the T-helper 9 cells. Here, we present evidence that T-helper 9 cells are dynamically increased with increasing the pathogenic strategy for hepatitis C virus (HCV). Furthermore, viral clearance is associated with a decrease in T-helper 9. The increase in T-helper 9 was paralleled with an increase in its receptor expression. Taken together, our data suggest that T-helper 9 cells play an important role in the pathogenesis of HCV, and is directly associated with HCV-related complications.

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“…In China, the majority of patients with HCC are also believed to be chronically infected with HBV, a conclusion that was drawn based on virus-free mouse models, which admittedly differ from HCC patients with HBV. The effects of whole-cell vaccine and HBV cross-interaction on Th9 cells should be further studied to identify possible dual effects of Th9 cells in HCC (40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Irradiated whole‑cell vaccine suppresses hepatocellular carcinoma growth in mice via Th9 cells

et al. 2021

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Decreased frequency of circulating Th9 cells in patients with chronic hepatitis B infection

Abstract: The depletion of Th9 cells is associated with the development of chronic HBV infection.

Cited by 13 publications

References 34 publications

Interleukin-35 Suppresses Interleukin-9-Secreting CD4+ T Cell Activity in Patients With Hepatitis B-Related Hepatocellular Carcinoma

Interleukin-35 Suppresses Interleukin-9-Secreting CD4+ T Cell Activity in Patients With Hepatitis B-Related Hepatocellular Carcinoma

Role of T-Helper 9 Cells in Chronic Hepatitis C-Infected Patients

Irradiated whole‑cell vaccine suppresses hepatocellular carcinoma growth in mice via Th9 cells

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