Hepatectomy leads to loss of TRAIL-expressing liver NK cells via downregulation of the CXCL9-CXCR3 axis in mice

PloS One
Takuya YanoHideki Ohdan

Abstract

Liver-resident natural killer (NK) cells express TNF-related apoptosis-inducing ligand (TRAIL), a critical molecule for NK cell-mediated tumor cell killing. We previously reported that TRAIL expression in liver NK cells decreases markedly after hepatectomy; however, the mechanism underlying this drastic alteration remains unknown. In this study, we assessed the role of chemokine signaling in liver-resident NK cells during the perioperative period of hepatectomy. The expression levels of various chemokine receptors on liver-resident NK cells and their associations with TRAIL expression were analyzed by flow cytometry. The expression of various intrahepatic chemokines/cytokines was analyzed after 70% hepatectomy in mice by quantitative RT-PCR and flow cytometry. We further investigated whether polyinosinic-polycytidylic acid (poly I:C)-induced NK cell activation could ameliorate TRAIL expression in the liver after 70% hepatectomy in CXCR3-/- and wild-type mice. TRAIL+ NK cells strongly and exclusively expressed CXCR3, and the expression of its ligand CXCL9 was significantly decreased in the liver after hepatectomy. The kinetics of hepatic CXCL9 expression resembled the changes in hepatic TRAIL+ NK cells after hepatectomy. Among l...Continue Reading

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Citations

Jun 14, 2018·PloS One·Ryosuke NakanoHideki Ohdan
Jan 27, 2021·Cytokine & Growth Factor Reviews·Xue Yao, Sandro Matosevic
May 13, 2021·Nature Reviews. Gastroenterology & Hepatology·Sheng CaoVijay H Shah

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Methods Mentioned

BETA
PCR
Protein Assay
FCS
flow cytometry

Software Mentioned

SPSS Statistics

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