Natural killer cell-dependent anti-fibrotic pathway in liver injury via Toll-like receptor-9

PloS One
Lina Abu-TairRifaat Safadi

Abstract

The toll-like receptor-9 (TLR9) agonist cytosine phosphate guanine (CpG), activates hepatic stellate cells (HSCs) and mediates fibrosis. We investigated the TLR9 effects on lymphocyte/HSCs interactions. Liver fibrosis was induced in wild-type (WT) mice by intra-peritoneal carbon-tetrachloride (CCl4) induction for 6 weeks. Fibrotic groups were intravenously treated by a vehicle versus CpG along last 2 weeks. Compared to vehicle-treated fibrotic WT, the in-vivo CpG-treatment significantly attenuated hepatic fibrosis and inflammation, associated with decreased CD8 and increased NK liver cells. In-vitro, co-cultures with vehicle-treated fibrotic NK cells increased HSCs proliferation (P<0.001) while their CpG-treated counterparts achieved a significant decrease. To investigate the role of lymphocytes, TLR9(-/-) mice induced-hepatic fibrosis were used. Although TLR9(-/-) mice manifested lower fibrotic profile as compared to their wild-type (WT) counterparts, senescence (SA-β-Gal activity) in the liver and ALT serum levels were significantly greater. In an adoptive transfer model; irradiated WT and TLR9(-/-) recipients were reconstituted with naïve WT or TLR9(-/-) lymphocytes. The adoptive transfer of TLR9(-/-) versus WT lymphocytes l...Continue Reading

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Citations

Jan 14, 2016·Nature Reviews. Gastroenterology & Hepatology·Felix Heymann, Frank Tacke
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Aug 8, 2018·Frontiers in Immunology·Paoline LaurentCécile Contin-Bordes

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Methods Mentioned

BETA
ELISA
FACS
flow cytometry
transfection

Software Mentioned

BD FACSDiva
Bioquant®
Bioquant

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