Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 12, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12967-014-0308-9
Keywords
Liver myofibroblasts; Natural killer cell; Immune-mediated liver injury; Liver failure; Hepatitis B
Categories
Funding
- National Science and Technology Major Project [2012ZX100020, 2012ZX10002004, 2012ZX10002007]
- China Postdoctoral Science Foundation [2013 M542228]
- Sun Yat-Sen University Clinical Research 5010 Program [2007029]
- National Natural Science Foundation of China [81202319, 30971356]
- Natural Science Fund of Guangdong province [S2012010009084, S2012040008104]
- New Teacher Fund of the Ministry of Education [20120171120103]
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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.
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