Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-alpha in patients with chronic hepatitis B.


BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by hepatitis B virus (HBV) infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis and liver cancer. Interferon-alpha (IFN-alpha) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-alpha on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-alpha therapy. Notably, we identified three CHB-specific cell subsets, Pro-infla CD14 + monocytes, Pro-infla CD16 + monocytes and IFN + CX3CR1- NK cells, which highly expressed pro-inflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-alpha treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-alpha treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-alpha-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-alpha, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

Authors: Jiang P, Jia H, Qian X, Tang T, Han Y, Zhang Z, Jiang L, Yu Z, Zheng L, Yu G, Cai H, Zhang S, Zhang X, Gu J, Ye C, Yang L, Lu Y, Liu H, Lu X, Jin C, Ren Y, Lu M, Xu L, Yu J, Jin X, Yang Y, Qian P,
Journal: Hepatology;2024 Jan 1;79(1):167-182 doi:10.1097/HEP.0000000000000524
Year: 2024
PubMed: PMID: 37368993 (Go to PubMed)