ReferenceID 6300
Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8+ T and NK cell function
Cell Mol Immunol
Pegylated interferon-alpha (PegIFNalpha) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood
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Record Fields
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- Reference Id
- 6300
- Evidence Id
- 22890
- Core Evidence Id
- 22890
- Source Reference Id
- 5874
- Herb2 Reference Id
- HBREF006671
- Subject Paper Key
- HBIN045587_33432062
- Pubmed Id
- 33432062
- Doi
- 10.1038/s41423-020-00601-8
- Paper Title
- Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8+ T and NK cell function
- Paper Abstract
- Pegylated interferon-alpha (PegIFNalpha) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNalpha therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNalpha therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-gamma, TNF-alpha, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3+CD8+ T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3+CD8+ T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-alpha in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNalpha therapy by impairing the effector functions of CD3+CD8+ T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-alpha responsiveness during CHB treatment.
- Journal
- Cell Mol Immunol
- Publish Year
- 2021
- Experiment Subject
- patient
- Experiment Type
- Clinical Experiment
- Phenotype Related
- Chronic Hbv Infection; Chronic Hepatitis B; Hepatitis B E-antigen
- Paper Title Cn
- Paper Title En
- Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8+ T and NK cell function
- Bilingual Status
- semi_complete