Hepatitis C virus mediated chronic inflammation and tumorigenesis in the Humanised Immune system and Liver mouse model

Zheng, Feng; Sze, Ching Wooen; Keng, Choong Tat; Al-Haddawi, Muthafar; Liu, M.; Tan, Sue Yee; Kwek, H.L.; Her, Zhisheng; Chan, Xue Ying; Barnwal, Bhaskar; Loh, El Wui; Tan, Thiam Chye; Chang, Kyong-Mi; Chen, Q.; Tan, Youwen

doi:10.1016/s0168-8278(17)30421-x

Cited by 2 publications

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“…Chronic hepatitis C (CHC) is a serious global health problem and more than 185 million individuals are estimated to be infected with the hepatitis C virus (HCV) globally. 1 CHC is a potential cause of liver cirrhosis and hepatocellular carcinoma. 2 Impairment of host immunity, especially the loss of HCV-specific cellular immune response, may lead to chronic infection.…”

Section: Introductionmentioning

confidence: 99%

Polarization of granulocytic myeloid‐derived suppressor cells by hepatitis C core protein is mediated via IL‐10/STAT3 signalling

Wang

Yü

et al. 2018

Journal of Viral Hepatitis

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Summary Myeloid‐derived suppressor cells (MDSCs) have been described as suppressors of T‐cell function in many malignancies. Impaired T‐cell responses have been observed in patients with chronic hepatitis C virus infection (CHC), which is reportedly associated with the establishment of persistent HCV infection. Therefore, we hypothesized that MDSCs also play a role in chronic HCV infection. MDSCs in the peripheral blood of 206 patients with CHC and 20 healthy donors were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) of healthy donors cultured with hepatitis C virus core protein (HCVc) were stimulated with or without interleukin 10 (IL‐10). Compared to healthy donors and certain CHC patients with sustained viral response (SVR), CHC patients without SVR presented with a dramatic elevation of G‐MDSCs with the HLA‐DR−/lowCD33+CD14−CD11b+ phenotype in peripheral blood. The frequency of G‐MDSCs in CHC patients was positively correlated with serum HCVc, and G‐MDSCs were induced from healthy PBMCs by adding exogenous HCVc. Furthermore, we revealed a potential mechanism by which HCVc mediates G‐MDSC polarization; activation of ERK1/2 resulting in IL‐10 production and IL‐10‐activated STAT3 signalling. Finally, we confirmed that HCVc‐induced G‐MDSCs suppress the proliferation and production of IFN‐γ in autologous T‐cells. We also found that the frequency of G‐MDSCs in serum was associated with CHC prognosis. HCVc maintains immunosuppression by promoting IL‐10/STAT3‐dependent differentiation of G‐MDSCs from PBMCs, resulting in the impaired functioning of T‐cells. G‐MDSCs may thus be a promising biomarker for predicting prognosis of CHC patients.

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Section: Introductionmentioning

confidence: 99%

Polarization of granulocytic myeloid‐derived suppressor cells by hepatitis C core protein is mediated via IL‐10/STAT3 signalling

Wang

Yü

et al. 2018

Journal of Viral Hepatitis

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show abstract

“…Além disso, a infecção pelo HCV estimula a inflamação hepática e sistêmica com produção de citocinas pró-inflamatórias que favorecem o processo de ruptura, erosão ou ulceração de placas coronarianas; entretanto, os mecanismos patogênicos de ligação entre a infecção pelo HCV e a aterogênese ainda não estão completamente esclarecidos. Além do mais, a infecção por HCV está associada a doenças metabólicas, em especial, ao aumento da resistência à insulina do tipo 2 que é uma condição pró-aterogênica 34,[46][47][48] .…”

Section: Patogênese E História Natural Da Doençaunclassified

Avaliação do risco e causas de óbito entre indivíduos diagnosticados com hepatite C através de exames de triagem para doação de sangue, no período de 1994 a 2016, em um hemocentro de São Paulo-SP

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Hepatitis C virus mediated chronic inflammation and tumorigenesis in the Humanised Immune system and Liver mouse model

Cited by 2 publications

References 47 publications

Polarization of granulocytic myeloid‐derived suppressor cells by hepatitis C core protein is mediated via IL‐10/STAT3 signalling

Polarization of granulocytic myeloid‐derived suppressor cells by hepatitis C core protein is mediated via IL‐10/STAT3 signalling

Avaliação do risco e causas de óbito entre indivíduos diagnosticados com hepatite C através de exames de triagem para doação de sangue, no período de 1994 a 2016, em um hemocentro de São Paulo-SP

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