Liver myofibroblasts from hepatitis B related liver failure patients may regulate natural killer cell function via PGE2

BACKGROUND: Natural 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: These 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 MATERIAL: The online version of this article (doi:10.1186/s12967-014-0308-9) contains supplementary material, which is available to authorized users.