Genetic landscape and immune mechanism of monocytes associated with the progression of acute-on-chronic liver failure

作者：Jia Yao, Tian Liu, Qiang Zhao, Yaqiu Ji, Jinjia Bai, Han Wang, Ruoyu Yao, Xiaoshuang Zhou, Yú Chen, Jun Xu · 发表于：Hepatology International · 年份：2023 · DOI：10.1007/s12072-022-10472-y · 被引用次数：32 · 研究领域：Liver Disease and Transplantation、Immune Response and Inflammation、Immune cells in cancer

OBJECTIVE: Acute-on-chronic liver failure (ACLF) has a high prevalence and short-term mortality. Monocytes play an important role in the development of ACLF. However, the monocyte subpopulations with unique features and functions in ACLF and associated with disease progression remain poorly understood. We investigated the specific monocyte subpopulations associated with ACLF progression and their roles in inflammatory responses using the single-cell RNA sequencing (scRNA-seq). METHODS: We performed scRNA-seq on 17,310 circulating monocytes from healthy controls and ACLF patients and genetically defined their subpopulations to characterize specific monocyte subpopulations associated with ACLF progression. RESULTS: Five monocyte subpopulations were obtained, including pro-inflammatory monocytes, CD16 monocytes, HLA monocytes, megakaryocyte-like monocytes, and NK-like monocytes. Comparisons of the monocytes between ACLF patients and healthy controls showed that the pro-inflammatory monocytes had the most significant gene changes, among which the expressions of genes related to inflammatory responses and cell metabolism were significantly increased while the genes related to cell cycle progression were significantly decreased. Furthermore, compared with the ACLF survival group, the ACLF death group had significantly higher expressions of pro-inflammatory cytokines (e.g., IL-6) and their receptors, chemokines (e.g., CCL4 and CCL5), and inflammation-inducing factors (e.g., HES4). A...