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.