Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Li, Tianyang; Yang, Yang; Song, Haiou; Li, Haijun; Cui, An; Liu, Yanhou; Su, Lishan; Crispe, Ian Nicholas; Tu, Zhengkun

doi:10.1002/jlb.2a0118-031rr

Cited by 29 publications

(28 citation statements)

References 43 publications

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“…It is obvious that liver NK cells via TRAIL and/or NKG2D signaling have a major role in the removal of activated hepatic stellate cells in fibrotic liver or liver cancerous cells as reported in a tetrachloride mouse model of hepatic fibrosis (69, 70). We cannot rule out the contribution liver resident ILC1 in these earlier studies via either cytokine secretion or TRAIL-induced killing of target cells as recently described for activated NK cells (71). Hence, specific host protective roles are assigned to ILC during immune response.…”

Section: Hepatic Nk Cells and Ilc1 In Nafld Developmentmentioning

confidence: 75%

Natural Killer Cells and Type 1 Innate Lymphoid Cells Are New Actors in Non-alcoholic Fatty Liver Disease

et al. 2019

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Obesity and associated liver diseases (Non Alcoholic Fatty Liver Disease, NAFLD) are a major public health problem with increasing incidence in Western countries (25% of the affected population). These complications develop from a fatty liver (steatosis) to an inflammatory state (steatohepatitis) evolving toward fibrosis and hepatocellular carcinoma. Lipid accumulation in the liver contributes to hepatocyte cell death and promotes liver injury. Local immune cells are activated either by Danger Associated Molecular Patterns (DAMPS) released by dead hepatocytes or by bacterial products (PAMPS) reaching the liver due to increased intestinal permeability. The resulting low-grade inflammatory state promotes the progression of liver complications toward more severe grades. Innate lymphoid cells (ILC) are an heterogeneous family of five subsets including circulating Natural Killer (NK) cells, ILC1, ILC2, ILC3, and lymphocytes tissue-inducer cells (LTi). NK cells and tissue-resident ILCs, mainly located at epithelial surfaces, are prompt to rapidly react to environmental changes to mount appropriate immune responses. Recent works have demonstrated the interplay between ILCs subsets and the environment within metabolic active organs such as liver, adipose tissue and gut during diet-induced obesity leading or not to hepatic abnormalities. Here, we provide an overview of the newly roles of NK cells and ILC1 in metabolism focusing on their contribution to the development of NAFLD. We also discuss recent studies that demonstrate the ability of these two subsets to influence tissue-specific metabolism and how their function and homeostasis are affected during metabolic disorders.

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Section: Hepatic Nk Cells and Ilc1 In Nafld Developmentmentioning

confidence: 75%

Natural Killer Cells and Type 1 Innate Lymphoid Cells Are New Actors in Non-alcoholic Fatty Liver Disease

et al. 2019

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“…In addition, NK cells play a key role in the limitation of liver fibrosis through cytotoxicity of activated HSC[71]. Our recent study found a novel mechanism by which NK cells kill HSCs through TRAIL-involved degranulation manner[72]. In HBV infection, HBV-induced suppressive monocytes induce NK cell differentiation into NK-reg with decreased production of IFN-γ and increased IL-10[11].…”

Section: Does Hbv-induced Immune Suppression Contribute To Liver Fibrmentioning

confidence: 99%

Immune suppression in chronic hepatitis B infection associated liver disease: A review

Yang

Zhou

et al. 2019

WJG

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112

109

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Hepatitis B virus (HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer (HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer (NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC), NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBV-induced immune dysfunction and HBV-related liver diseases are not understood. In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.

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“…However, this hypothesis should be confirmed by testing a larger number of samples. The regulation between TRAIL and TANCR in NK cells should be validated due to TRAIL is also considered as a NK cell cytokine [40,41]. The current study focused on regulation occurring in cis, while lncRNAs can also regulate gene expression in trans or directly interact with proteins [13].…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA TANCR promotes γδ T cells activation by regulating TRAIL expression in cis

et al. 2020

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Background: γδ T cells are an important subset of T lymphocytes that play important roles in innate and adaptive immunity via the secretion of various cytokines. Previous studies have found that long noncoding RNAs (lncRNAs) are critical regulators that contribute to the development of immune cells. However, the functions of lncRNAs in the γδ T cells remains poorly studied. Results: Here, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)activated and-expanded γδ T cells using RNA-seq. As it functioned as an activating noncoding RNA of tumor necrosis factor related apoptosis-inducing ligand (TRAIL), an important cytotoxic cytokine that expressed by γδ T cells in responding to various infectious agents, we named this lncRNA as TANCR. Secondly, the expression of TANCR was found to be positively correlated with TRAIL expression in IPP activated γδ T cells. In addition, TANCR was confirmed to localized both in nucleus and cytoplasm. Finally, a loss-of-function was conducted by using siRNA/ASO or CRISPR/ Cas9 system to knockdown or knockout TANCR, and confirmed that silencing of TANCR inhibits TRAIL expression in several kinds of cells, including HEK293T cells, Jurkat cells, and primary γδ T cells. Conclusion: These evidences demonstrate that TANCR play important roles in γδ T cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδ T cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.

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Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Cited by 29 publications

References 43 publications

Natural Killer Cells and Type 1 Innate Lymphoid Cells Are New Actors in Non-alcoholic Fatty Liver Disease

Natural Killer Cells and Type 1 Innate Lymphoid Cells Are New Actors in Non-alcoholic Fatty Liver Disease

Immune suppression in chronic hepatitis B infection associated liver disease: A review

Long noncoding RNA TANCR promotes γδ T cells activation by regulating TRAIL expression in cis

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