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Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL‐involved degranulation manner
Author(s) -
Li Tianyang,
Yang Yang,
Song Hongxiao,
Li Haijun,
Cui An,
Liu Yanhou,
Su Lishan,
Crispe Ian Nicholas,
Tu Zhengkun
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2a0118-031rr
Subject(s) - degranulation , biology , microbiology and biotechnology , hepatic stellate cell , cytotoxic t cell , pi3k/akt/mtor pathway , protein kinase b , signal transduction , interleukin 21 , cancer research , immune system , immunology , t cell , receptor , biochemistry , endocrinology , in vitro
Abstract NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL‐12 and IL‐18, and innate immune stimuli such as ligation of TLRs. The secretion of IL‐18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL‐18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL‐18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38/PI3K/AKT pathway, and that the activated NK cells mediate HSC death in a TRAIL‐involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38/PI3K/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression.