title: Elevated circulating CD14lowCD16+monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization.
abstract: Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease in which monocytes/macrophages infiltration and skewed T helper type (Th) 1 and Th17 cell responses participate in the development of the disease. Human peripheral blood monocytes are heterogeneous and can be divided into classical CD14highCD16-, intermediate CD14highCD16+, and nonclassical CD14lowCD16+monocyte subsets. Compared to classical monocytes, CD16+monocytes are generally termed pro-inflammatory monocytes and play an important pathogenic role in autoimmune diseases. However, little is known about the immunophenotype and immunopathogenic role of peripheral blood CD16+monocytes in PBC. Thus, we investigated the phenotype and function of these circulating monocyte subsets from PBC patients. The frequencies of circulating CD14highCD16+and CD14lowCD16+subpopulation were increased in disease compared with healthy controls. Among them, CD14lowCD16+monocyte subset positively correlated with disease progress, liver damage indicators and serum C-reactive protein, respectively. Furthermore, the frequencies of Th1 and Th17 cells were upregulated and CD14lowCD16+monocyte subset was also positively associated with Th1 cell frequency in PBC. Using a vitro coculture model, we further found that CD14lowCD16+monocytes promoted Th1 cell polarization compared to classical monocytes. Interleukin-12 (IL-12) and direct contact of patient CD4+T cell and CD14lowCD16+monocytes, were responsible for CD14lowCD16+monocytes promotion of Th1 cells polarization in PBC. Our study demonstrated that the enhanced CD14lowCD16+monocyte subset participated in fostering liver damage and inflammatory responses, and promoted Th1 cells skewing in PBC.
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Anping
authors.initials: A
authors.lastname: Peng
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Ke
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China.
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hepatology, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Pathogenic Biology and Immunology, Institute of Immunology, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzanno, Italy.|Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA.
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Biological Resource Center, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. qubochen326@163.com.
authors.forename: Qubo
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China. Zjh2208@163.com.
authors.forename: Junhua
authors.initials: J
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D002097:C-Reactive Protein
keywords: CD16; Monocyte subsets; Primary biliary cirrhosis; T helper type 1 cells