Open AccessAcute portal hypertension using portal vein ligation abrogates TRAIL expression of liver‐resident NK cells
Author(s) -
Imaoka Yuki,
Sato Koki,
Ohira Masahiro,
Imaoka Kouki,
Yano Takuya,
Nakano Ryosuke,
Tanaka Yuka,
Ohdan Hideki
Publication year - 2022
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.2017
Subject(s) - cytotoxic t cell , cancer research , tumor necrosis factor alpha , interleukin 21 , lymphokine activated killer cell , interleukin 12 , janus kinase 3 , protein kinase b , cytokine , mapk/erk pathway , immune system , immunology , medicine , biology , t cell , signal transduction , microbiology and biotechnology , biochemistry , in vitro
Abstract The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver‐resident NK (lr‐NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL + ) lr‐NK cells by about 20% and attenuated cytotoxic activity against the Hepa1‐6 cell line by about 40%. Among various cytokine, only interleukin‐33 (IL‐33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr‐NK cells highly expressed ST2/IL‐33R, IL‐33 co‐culture significantly suppressed TRAIL expression on lr‐NK cells by about 50%, and IL‐33 administration markedly decreased TRAIL expression and cytotoxic activity of lr‐NK cells. Furthermore, the TRAIL + NK cells population was maintained by anti‐IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL‐33 decreased TRAIL expression in lr‐NK cells via AKT–forkhead box O (FoxO) and mitogen‐activated protein kinase (MAPK) signaling. Conclusion : This work demonstrates that PHT suppresses the TRAIL + lr‐NK cell population and antitumor activities in the liver. Additionally, Akt‐FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt‐NK cells via IL‐33 receptor in mice.