Entecavir-induced interferon-λ1 suppresses type 2 innate lymphoid cells in patients with hepatitis B virus-related liver cirrhosis
| Autor: | Shengdi Wu, Wei-min She, Wei Jiang, Yun Liu, Yue Shen, Jing Li, Li-Sha Cheng, Si-Qi Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Liver Cirrhosis
Hepatitis B virus Cirrhosis Guanine medicine.medical_treatment Receptor expression medicine.disease_cause Antiviral Agents 03 medical and health sciences Liver disease 0302 clinical medicine Hepatitis B Chronic Interferon Virology medicine Humans 030212 general & internal medicine Lymphocytes Hepatology business.industry Innate lymphoid cell Entecavir medicine.disease Immunity Innate Infectious Diseases Cytokine Immunology Leukocytes Mononuclear 030211 gastroenterology & hepatology Interferons business medicine.drug |
| Zdroj: | Journal of viral hepatitisREFERENCES. 28(5) |
| ISSN: | 1365-2893 |
| Popis: | The immunomodulatory effects of entecavir (ETV) in anti-hepatitis B virus (HBV) therapy have long been recognized. This study aimed to determine the effects of ETV on non-natural killer innate lymphoid cells (non-NK ILCs) in HBV-related liver disease progression. We enrolled treatment-naive chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) patients treated with ETV for 24 months. Before and after therapy, the frequency and cytokine profiles of ILC2s and non-NK ILCs subset homeostasis and their clinical significance were determined, and serial serum interferon (IFN)-λ levels were analyzed. Peripheral blood mononuclear cells (PBMCs) of untreated LC patients were cultured with serum from untreated and ETV-treated LC patients in addition to being subject to IFN-λ1 neutralization and stimulation, and the frequency and cytokine production of ILC2s as well as non-NK ILCs subset ratios were calculated. Furthermore, IFN-λ receptor expression on non-NK ILCs and dendritic cells (DCs) was measured. After 24 months of ETV treatment, the frequency and cytokine production of ILC2s (IL-4, IL-13, IFN-γ, TNF-α) decreased with increased ILC1/ILC2 and decreased ILC2/ILC3 ratios, revealing a close association with disease status in LC patients. Long-term ETV administration induced serum IFN-λ1 levels were negatively correlated with ILC2s. ETV-treated LC serum culture and IFN-λ1 stimulation yielded similar effects on suppression of ILC2s, and IFN-λ1 neutralization in serum culture partly inhibited this effect. The IFN-λ receptor was detected on DCs but not on non-NK ILCs. In conclusion, ETV suppresses the frequency and cytokine profiles of ILC2s by increasing IFN-λ1 in LC patients. |
| Databáze: | OpenAIRE |
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