Reduced Proportion of CD39+ Treg Cells Correlates with the Development of Primary Biliary Cholangitis in Patients and a Murine Model

Abstract

Primary Biliary Cholangitis (PBC) is a chronic autoimmune cholestatic liver disease. This study investigated changes of adenosine metabolism pathway related molecules and their contribution to inflammatory injury in PBC. Clinical results showed that the concentrations of alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and g-Glutamyl Transferase (GGT) in serum of 64 PBC subjects increased compared with 60 Healthy Controls (HC). The proportion of CD39+CD4+ cells was decreased in PBMCs from PBC patients in comparsion to HC. Moreover, the proportion of CD39+ Treg cells in PBMCs from PBC patients also significantly decreased in comparsion to HC. A PBC murine model results showed that, compared with the normal mice, the concentrations of ALT, AST and GGT in serum significantly increased induced by polyinosinic-polycytidylic acid (poly I:C). Histopathology result revealed that poly I:C induced liver inflammation in mice. The proportion of CD39+ cells in PBMCs from poly I:C-treated mice was decreased compared with the normal mice. Meanwhile, the proportions of CD39+CD4+ cells and CD39+Treg cells were markedly reduced in poly I:C-induced mouse spleen. Finally, poly I:C significantly induced a global reduction of CD39 and adenosine receptor A2a expression in mouse liver. In addition, poly I:C treatment didn’t alter the proportions of CD39+CD8+ and CD39+CD19+ cells in mouse liver. In conclusion, our results suggest that the proportion of CD39+ Treg cells decreasing in PBC patients and animal model are closely associated with the disease progression. Our study offers a novel perspective on the role of adenosine metabolism pathway in PBC pathogenesis.