Abstract
BackgroundNatural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury. However, few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related liver failure (LF), and the precise mechanism underlying NK cell regulation is not fully understood.MethodsWe detected the percentage and function of peripheral NK cells both in hepatitis B related LF patients and healthy volunteers by flow cytometry and isolated the liver myofibroblasts (LMFs) from hepatitis B related LF livers. To determine the possible effects of LMFs on NK cells, mixed cell cultures were established in vitro.ResultsWe found a down-regulated percentage of peripheral NK cells in hepatitis B related LF patients, and their NK cells also displayed decreased activated natural cytotoxicity receptors (NCRs) and cytokine production. In a co-culture model, LMFs sharply attenuated IL-2-induced NK cell triggering receptors, cytotoxicity, and cytokine production. The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2.ConclusionThese data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0308-9) contains supplementary material, which is available to authorized users.
Highlights
Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury
Blood were from 20 patients with hepatitis B induced liver failure (Additional file 1: Table S1) and 20 healthy individuals as controls; diseased liver tissues were from 4 patients undergoing transplantation for hepatitis B induced LF (Additional file 1: Table S1); healthy livers were from 3 patients undergoing surgery for hepatic hemangioma; normal skin fibroblasts (NFs) were from 2 patients undergoing circumcision
The percentage of peripheral NK cells are decreased with dysfunction in hepatitis B related LF patients To better understand the potential role of NK cells in the pathogenesis of hepatitis B related LF, we first detected the distribution and phenotype of peripheral NK cells in these patients
Summary
Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury. Few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related liver failure (LF), and the precise mechanism underlying NK cell regulation is not fully understood. The production of IFN-γ and TNF-α, a hallmark of NK cell activation, is another important mechanism contributing to liver injury, which occurs through the induction of hepatocyte apoptosis and activation/recruitment of other immune effector cells [12,15,16]. Few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related LF, and the precise mechanism underlying NK cell regulation is not fully understood
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