Role of interleukin-21 in HBV infection: friend or foe?

Li, Yongyin; Tang, Libo; Hou, Jinlin

doi:10.1038/cmi.2014.109

Cited by 23 publications

(20 citation statements)

References 52 publications

(80 reference statements)

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“…The broad immunomodulatory activity of IL‐21 is critical in chronic viral infections . IL‐21 promotes proliferation of Tfh and Th17 lymphocytes, enhances the cytotoxicity of CD8 + T cells and NK cells, and induces differentiation of the B lymphocytes into plasma cells .…”

Section: Introductionmentioning

confidence: 99%

“…IL‐21 also plays a key regulatory role in HBV infection pathogenesis. High serum IL‐21 levels are associated with a high model for end‐stage liver disease (MELD) score and mortality rates . In the mouse model of HBV, IL‐21 regulates specific CD8 + T‐ and B‐lymphocyte responses that are crucial for the clearance of the viral antigens .…”

Section: Introductionmentioning

confidence: 99%

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Interleukin‐21 receptor gene polymorphism is associated with hepatitis B virus‐related hepatocellular carcinoma in Chinese patients

Liu

Song

Zhang

et al. 2019

Clinical Laboratory Analysis

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BackgroundWe investigated the relationship between hepatitis B virus (HBV)‐related pathogenesis and single nucleotide polymorphisms (SNPs) in interleukin‐21 (IL‐21)‐JAK‐STAT signaling pathway genes.MethodsWe used the high‐resolution melting (HRM) method to genotype five SNPs (IL‐21 rs2221903, IL‐21 rs4833837, IL‐21 receptor (IL‐21R) rs2285452, JAK3 rs3008, and STAT3 rs1053023) in 546 HBV‐infected patients and 353 healthy Chinese subjects. The HBV‐infected patients were further divided into subgroups based on the HBV‐related pathologies: chronic hepatitis B (CHB), HBV‐related liver cirrhosis (LC), and HBV‐related hepatocellular carcinoma (HCC).ResultsThere were no significant differences in the genotype and allele distributions of the five SNPs between the HBV‐infected patients and healthy subjects. The genotype and allele frequencies were similar in the two groups for IL‐21 rs2221903 (A>G, P = 0.83 and 0.67), rs4833837 (A>G, P = 0.80 and 0.49), IL‐21R rs2285452 (G>A, P = 0.25 and 0.68), STAT3 rs1053023 (A>G, P = 1.00 and 0.96), and JAK3 rs3008 (C>T, P = 0.32 and 0.54). However, patients with the IL‐21R rs2285452 AA genotype were more susceptible to HBV‐related HCC than those with the IL‐21R rs2285452 GA/GG genotype (P = 0.03, OR = 3.27, 95% CI = 1.16‐9.20). The serological marker model of “HBsAg+, HBeAg+, HBcAb+” was predominant among patients with HBV infection. However, there was no association between the genotype's distribution of the five SNPs and the serological marker models (P > 0.05).ConclusionsThese findings demonstrate that the IL‐21R rs2285452 AA genotype increases the risk of HBV‐related HCC in Chinese patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interleukin‐21 receptor gene polymorphism is associated with hepatitis B virus‐related hepatocellular carcinoma in Chinese patients

Liu

Song

Zhang

et al. 2019

Clinical Laboratory Analysis

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“…The broad immunomodulatory activity of IL-21 is critical in chronic viral infections [14]. IL-21 promotes proliferation of Tfh and Th17 lymphocytes, enhances the cytotoxicity of CD8 + T cells and NK cells, and induces differentiation of the B-lymphocytes into plasma cells [15].…”

Section: Introductionmentioning

confidence: 99%

“…IL-21 also plays a key regulatory role in HBV infection pathogenesis. High serum IL-21 levels are associated with a high model for end-stage liver disease (MELD) score and mortality rates [14]. In the mouse model of HBV, IL-21 regulates specific CD8 + T-and B-lymphocyte responses that are crucial for the clearance of the viral antigens [16].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Interleukin-21 receptor gene polymorphism is associated with hepatitis B virus-related hepatocellular carcinoma in Chinese patients

Liu¹,

Zhang²,

Song³

et al. 2018

Oncotarget

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“…IL-15 also inhibited HBV replication via IFN-β production and exerted anti-HBV functions independent of γc receptor in mouse model (Yin et al, 2012). IL-21, which derived from HBV-specific CD4 + T cells, played viral roles in sustaining viral-specific CD8 + T cells and promoting B cell response (Li et al, 2015), although our previous studies showed that IL-21 did not enhance HBV-specific immune response in mouse models (Zhang et al, 2014). Importantly, high serum IL-21 levels after 12 weeks of telbivudine therapy predicted HBeAg seroconversion in CHB (Ma et al, 2012).…”

Section: Discussionmentioning

confidence: 94%

Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection

Dong

Yang

Wang

et al. 2017

Front. Cell. Infect. Microbiol.

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T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study. Tim-3 expressions on CD4+ and CD8+ T cells were assessed in response to HBV-encoding antigens, HBV peptide pools, and common γ-chain (γc) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28 directly induced Tim-3 expression on T cells. γc cytokines also drive Tim-3 up-regulations on both CD4+ and CD8+ T cells in patients with chronic HBV infection. However, γc cytokines did not enhance the Tim-3 inductions by either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, γc cytokines-mediated Tim-3 induction could not be abrogated by γc cytokine receptor-neutralizing antibodies. The current results suggested that elevation of Tim-3 expression on T cells could be regulated by both antigen-dependent and -independent manner in patients with chronic HBV infection. The role of γc cytokines in modulation of inhibitory pathway might be evaluated as immunotherapies in humans.

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Role of interleukin-21 in HBV infection: friend or foe?

Cited by 23 publications

References 52 publications

Interleukin‐21 receptor gene polymorphism is associated with hepatitis B virus‐related hepatocellular carcinoma in Chinese patients

Interleukin‐21 receptor gene polymorphism is associated with hepatitis B virus‐related hepatocellular carcinoma in Chinese patients

WITHDRAWN: Interleukin-21 receptor gene polymorphism is associated with hepatitis B virus-related hepatocellular carcinoma in Chinese patients

Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection

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