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

Abstract

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.

MiR-155-5p modulates HSV-1 replication via the epigenetic regulation of SRSF2 gene expression

“…In addition, researchers have found that miR-155-5p mediates T lymphocyte differentiation [26] and inhibits cell apoptosis [27]. In pathogenesis, miR-155-5p is associated with many diseases, such as cancer [28,29], cardiovascular disease [30], autoimmune disease [31], metabolic disease [32], and neurological disorders [33]. During HSV-1 infection, several studies have shown that the expression level of miR-155-5p is markedly increased by the viral infection [34,35].…”

Propofol Promotes Activity and Tumor-Killing Ability of Natural Killer Cells in Peripheral Blood of Patients with Colon Cancer

“…Studies show that NK cell surface receptors, killing effector molecules, and proliferation are regulated at multiple levels, such as miRNA, lncRNA, or Jak-Stat signaling pathway. We hypothesize that propofol may be involved in the regulation of NK cells at these levels, but the specific mechanisms remain to be further studied [ 42 , 43 ].…”

Noncoding RNA in NK cells

“…A recent study of immune‐active patients among those with hepatitis B virus (HBV) infection found the miR‐155, a positive regulator of IFN‐γ in NK cells, was expressed much lower in patients than in healthy controls. In response to HBV infection in patients, down‐regulation of miR‐155 impaired IFN‐γ secretion through targeting suppressor of cytokine signaling 1 (SOCS1) in the JAK/STAT signaling pathway . Positive regulators of IFN‐γ, such as miR‐181[54] and miR‐155, together with the negative regulator miR‐146, balance the expression of IFN‐γ in NK cells during the immune response.…”