Elevated circulating CD14lowCD16+ monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization

Anping Peng, Peifeng Ke, Rong Zhao, Xinyi Lu, Cheng Zhang, Xianzhang Huang, Guangjun Tian, Jun Huang, Jinli Wang, Pietro Invernizzi, Qubo Chen, Junhua Zhuang

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
JournalClinical and Experimental Medicine
DOIs
StateAccepted/In press - Sep 24 2015

Keywords

  • CD16
  • Monocyte subsets
  • Primary biliary cirrhosis
  • T helper type 1 cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Peng, A., Ke, P., Zhao, R., Lu, X., Zhang, C., Huang, X., Tian, G., Huang, J., Wang, J., Invernizzi, P., Chen, Q., & Zhuang, J. (Accepted/In press). Elevated circulating CD14lowCD16+ monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization. Clinical and Experimental Medicine. https://doi.org/10.1007/s10238-015-0381-2