Despite their importance in liver wound healing, it is hypothesized that activated HSCs may encourage pathogenesis during liver fibrosis. Upon liver injury, HSCs, the major source of collagen in the liver, transdifferentiate from quiescent lipocytes into myofibroblast-like cells to drive fibrogenesis, which is characterized by enhanced chemotaxis, survival and collagen production ( 4, 8, 9). Accumulating evidence has revealed the critical role of activated hepatic stellate cells (HSCs) in collagen and extracellular matrix (ECM) production ( 3, 6, 7). The condition mainly results from chronic liver inflammation, often induced by virus-associated hepatitis, drug/alcohol abuse, or autoimmune liver disease, and features excess accumulation of extracellular matrix subsequent to chronic liver injury ( 3– 5). Liver fibrosis, a common final pathway for most chronic liver diseases, poses a threat to public health worldwide, accounting for more than 1 million deaths each year ( 1, 2). Our findings reveal the landscape and dynamics of single immune cells in liver fibrosis, and clarify the protective role of TCR IR in response to chronic liver injury. Interestingly, a deficiency of TCR IR (Tcrb KO mice) led to a deterioration of liver fibrosis, coupled with activation of hepatic stellate cells (HSCs) induced by the upregulation of macrophage and γδ T cell distribution in fibrotic Tcrb KO livers. The results from scRNA-seq and bulk immune repertoire sequencing (IR-seq) revealed an obvious decline in T cell receptor (TCR) clonotypes combined with shrinking VJ and VDJ segment usage, as well as lower complementarity-determining region 3 (CDR3) amino acid (AA) diversity from fibrotic liver. Furthermore, we uncovered a novel fibrosis-associated CD8 T ( Ccl5 +, Ccl4 +) and CD4 T ( mt-Co1 +) cell subpopulation, which infiltrates fibrotic liver and is characterized by abnormal activation or inactivation as well as a TCR decline. In addition, we report changes in the transcriptomes of diverse immune cell types, implying a deteriorating intrahepatic immune microcircumstance. Analysis of approximately 10,000 single-cell transcriptomes revealed an increase in dendritic cells (DCs), macrophages, and neutrophils and a decrease in T and natural killer T (NKT) cells. In this study, we profiled the transcriptomes of intrahepatic CD45 + immune cells, from mice, using single-cell RNA sequencing (scRNA-seq) technology to understand the landscape of intrahepatic immune cells during the pathogenesis of fibrosis. 5Department of Gynaecology and Obstetrics, The 971 Hospital of People’s Liberation Army Navy, Qingdao, ChinaĪberrant immune cell infiltrates and microcircumstances represent characteristic features of liver fibrosis.4Department of Pathology, Qingdao Municipal Hospital, Qingdao, China.3Department of Pathology, The 971 Hospital of People’s Liberation Army Navy, Qingdao, China.2State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.1National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, China.Qing Liang 1†, Yudi Hu 1†, Meina Zhang 1, Chunjie Lin 2, Wei Zhang 3, Ying Li 4, Ping Zhu 5, Pengxin Xue 1, Yujie Chen 1, Qiyuan Li 1 and Kejia Wang 1*
0 kommentar(er)
