The Multiple Facets and Disorders of B Cell Functions in Hepatitis B Virus Infection

Ablikim, Dilhumare; Zeng, Xiangyong; Xu, Chunli; Zhao, Mengxiao; Yang, Xuecheng; Feng, Xuemei; Liu, Jia

doi:10.3390/jcm12052000

Cited by 2 publications

(1 citation statement)

References 125 publications

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“…In chronic HBV, a new subset of regulatory B (Breg) cells that can regulate CD8+T cell immunity and produce IL-10 was identified. Increased IL-10 levels with Breg cell number in chronic HBV were associated with viral load and liver inflammation dynamics 9 . In support of this information, IL10 SNPs have been reported to be associated with the chronicity of hepatitis B and liver damage caused by HBV 10 .…”

Section: Introductionmentioning

confidence: 99%

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

Temel

Akçam

Caner

et al. 2023

Rev. Assoc. Med. Bras.

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OBJECTIVE: Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. METHODS: The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. RESULTS: A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0. 0351 and p=0.032, respectively). CONCLUSION: This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

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Section: Introductionmentioning

confidence: 99%

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

Temel

Akçam

Caner

et al. 2023

Rev. Assoc. Med. Bras.

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RNAi-mediated HBV antigen shutdown enhances the antiviral immune effects of PEGIFNα via altering T and B cell crosstalk

Zai,

Hu,

et al. 2024

Preprint

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PEGylated interferon-α (PEGIFNα) demonstrates promising therapeutic outcomes against chronic hepatitis B (CHB), whereas patient response to PEGIFNα therapy remains unsatisfied. Shutdown of hepatitis B virus (HBV) antigens by RNA interference (RNAi) could enhance PEGIFNα efficacy in CHB patients, whereas the underlying immunological mechanisms remain obscure. We performed studies by utilizing our newly established extracellular humanized IFNAR (IFNAR-hEC) mice. An in-house constructed small interfering RNAs (GalNac-siHBV) was administrated to mice either alone or in combination with PEGIFNα. The phenotypic and functional characteristics of peripheral and organ-specific immune cells were assessed by flow cytometry, ELISpot, RNA sequencing (RNA-seq), and single-cell RNA-seq (scRNA-seq) analysis. Our results demonstrated that combined treatment with PEGIFNα and RNAi exerted a synergistic and prolonged inhibition of HBsAg (∼4log10IU/mL, vs PBS) and induced a higher incidence of HBsAg seroconversion (∼30%), comparing with either monotreatment. Mechanistically, combined therapy improved the functionality of global T and B cells, triggered increased anti-HBs producing B cells, and enhanced IFNγ-producing T cells. scRNA-seq analysis revealed that the combined therapy reduced inhibitory B cell-B cell interaction, enhanced MHC-I signaling mediated T cell-T cell communication, and improved T cell-B cell crosstalk, thus improving the functionality of T and B cells. Enhanced MHC-II signaling networks across B cells and hepatocytes/Cd8+T cells further promoted HBsAg seroconversion in the combined treatment groups. These results together provided scientific rationale and lessons for the combination of the two towards better therapeutic efficacy.Graphical AbstractHighlightsShutting down HBsAg through RNA interference augmented the antiviral immune effects of PEGIFNα in chronic HBV-carrier IFNAR-hEC mice.Combined RNAi plus PEGIFNα augmented the functionality of T cells, promoted B cell activation and class switch, but also exerted some suppressive effects on B cells.Reduced inhibitory B cell-B cell interaction, enhanced MHC-I signaling between T cells and T cells, and improved T cell-B cell crosstalk, improved the functionality of T cells and B cells.Enhanced MHC-II signaling networks across B cells and hepatocytes/ Cd8+T cells further promoted HBsAg seroconversion in RNAi plus PEGIFNα combined treatment groups.

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The Multiple Facets and Disorders of B Cell Functions in Hepatitis B Virus Infection

Cited by 2 publications

References 125 publications

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

RNAi-mediated HBV antigen shutdown enhances the antiviral immune effects of PEGIFNα via altering T and B cell crosstalk

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