Background & Aims: Natural killer (NK) cells are anti-tumor and anti-fibrotic protectors in the innate immunity. However, impaired NK cell killing reported in cirrhosis and some tumors. We found Neuroligin-4 (NLG4) gene expression on NK cells of liver injured patients from different etiologies were elevated including NAFLD and was associated with decreased in NK cytotoxicity. In this study, we aim to explore variations of NLG4 expressions on NK subpopulation (conventional NK cells CD49a- CD49b+) in liver and peripheral blood (PB) as a modulation of NK cells activity in fibrotic mice. Methods: NK cells isolated from peripheral blood lymphocytes and livers of C57/BL induced fibrosis by Carbon-tetrachloride (CCl4) injections (2X/wk for 2 weeks). NLG4 receptor expressions and NK activation marker (CD107, LAMP1- Lysosomal-associated membrane protein 1) on conventional populations assessed by CD49a- CD49b+ were determined by flow cytomerty technique. Results: Liver NK cells expressing CD49a- CD49b+ were 17%±1.4% in naïve mice as compared to 36±3.6% in fibrotic counterparts. PB NK cells expressing CD49a- CD49b+ were 27%±4.3% in naïve mice as compared to 30±2.7% in fibrotic mice. While the liver NK cells of the naïve mice expressed 10±1.2% NLG4 receptor, the NK cells of the fibrotic mice had significant elevations of NLG4 receptor (71±9.1% ; P<0.02). These results were accompanied with a prominent decrease in % NK activation marker-CD107a in the fibrotic mice (P<0.01). In parallel, PB NK cells from fibrotic mice had slight elevations in NLG4 receptor of 10±9.1% as compared to the naïve mice (4.1±0.6%) (P=0.04). However, no elevations of PB NK NLG4 receptor were seen following CCl4 injections. Conclusion: Conventional NK cells although are dominated in the PB of mice as compared to livers showed to express low NLG4 receptors with no significant modulations in their functionality impairment and point to the role of liver conventional NK cells in attenuating/promoting liver fibrosis.

Conference Title

European Association for Study of Liver -EASL

Conference Country

Spain

Conference Date

April 13, 2016 - April 17, 2016

Conference Sponsor

EASL