Analysis of liver NK cell activation mechanisms through CXCL9/CXCR3 chemokine axis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19893
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: Ohira Masahiro 広島大学, 病院(医), 病院助教 (30397947)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: NK細胞 / TRAIL / ケモカイン / 肝切除 / 肝癌

Outline of Final Research Achievements

Liver resident natural killer (NK) cells express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a critical molecule for NK cell-mediated tumor cell killing.
TRAIL+ NK cells strongly and exclusively expressed CXCR3. CXCL9, a ligand of CXCR3, was significantly decreased in the liver after hepatectomy. The kinetics of hepatic CXCL9 expression resembled those of hepatic TRAIL+ NK cell proportions after hepatectomy. Among liver-resident mononuclear cells, macrophages predominantly secreted CXCL9 in response to interferon (IFN)-gamma stimulation. Although the administration of poly I:C, an inducer of IFN-gamma, increased hepatic CXCL9 levels in both CXCR3-/- and WT mice, even after hepatectomy, only WT mice recovered TRAIL expression on NK cells. Major hepatectomy remarkably reduced the proportion of TRAIL-expressing NK cells in the liver through downregulation of the CXCL9-CXCR3 axis in mice.

Free Research Field

肝胆膵移植外科