Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer Cells in Patients with Chronic...

MicroRNAs have been reported to be regulated in different ways in a variety of liver diseases. As a key modulator of cellular function in both innate and adaptive immunity, the role of miR-155 in chronic hepatitis B virus infection remains largely unknown. Here, we investigated the expression and function of miR-155 in chronic hepatitis B (CHB) patients. It was found that miR-155 expression in peripheral blood mononuclear cells (PBMCs) was lower in CHB patients than healthy controls (HC). Among CHB infection, immune-active (IA) patients with abnormal alanine aminotransferase (ALT) levels had relatively higher miR-155 expression in PBMCs and serum than immune-tolerant carriers, but were comparable to inactive carriers. Moreover, there was a positive correlation between miR-155 expression and ALT levels in CHB patients. Particularly, miR-155 expression in natural killer (NK) cells was significantly downregulated in IA patients compared with HC. Inversely, suppressor of cytokine signaling 1 (SOCS1), a target of miR-155, was upregulated in NK cells of IA patients. Overexpression of miR-155 in NK cells from IA patients led to a decrease in SOCS1 expression and an increase of IFN-γ production. Finally, accompanied by the normalization of ALT, miR-155 expression in PBMCs gradually decreased during telbivudine or peg-IFN-α-2a therapy. Interestingly, higher miR-155 expression at baseline was associated with better response to telbivudine therapy, but not peg-IFN-α-2a. In conclusion, our data suggested that miR-155 downregulation in NK cells of IA patients impaired IFN-γ production by targeting SOCS1, which may contribute to immune dysfunction during CHB infection. Additionally, baseline miR-155 expression could predict the treatment response to telbivudine therapy.