NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis

Nilsson, Julia; Hörnberg, Maria; Schmidt-Christensen, Anja; Linde, Kajsa; Nilsson, Mikael; Carlus, Marine; Erttmann, Saskia F.; Mayans, Sofia; Holmberg, Dan

doi:10.1038/s41598-020-78688-2

Cited by 15 publications

(13 citation statements)

References 54 publications

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“…Inflammasome activation in natural killer (NK) cells promotes HSC apoptosis and alleviates the progression of liver fibrosis in a TRAIL-dependent degranulation manner ( 124 ). In contrast, natural killer T (NKT) cells had dual roles in regulating liver fibrosis via activating the NLRP3 inflammasome ( 125 ). Besides, the NLRC4 inflammasome in neutrophils initiated auto-inflammatory disease, and these effects were attenuated in Asc knockout mice or after IL-1 receptor inhibitor administration ( 126 ).…”

Section: Inflammasome and Pyroptosis In Liver Fibrosismentioning

confidence: 99%

Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis

et al. 2022

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Inflammasomes are multiprotein complexes that can sense danger signals and activate caspase-1 to mediate pro-inflammatory cytokines release and pyroptotic cell death. There are two main canonical and non-canonical signaling pathways that trigger inflammasome activation. Inflammasomes are expressed and assembled in parenchymal and nonparenchymal cells in response to liver injury in the liver. Additionally, the hepatocytes, biliary epithelial cells (cholangiocytes), hepatic stellate cells (HSCs), hepatic macrophages, and liver sinusoidal endothelial cells (LSECs) contribute to liver fibrosis via different mechanisms. However, the underlying mechanism of the inflammasome and pyroptosis in these liver cells in liver fibrosis remains elusive. This review summarizes the activation and function of inflammasome complexes and then discusses the association between inflammasomes, pyroptosis, and liver fibrosis. Unlike other similar reviewers, we will focus on the effect of inflammasome activation and pyroptosis in the various liver cells during the development of liver fibrosis. We will also highlight the latest progress of pharmacological intervention in inflammasome-mediated liver fibrosis.

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Section: Inflammasome and Pyroptosis In Liver Fibrosismentioning

confidence: 99%

Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis

et al. 2022

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“…In addition, activated iNKT cells could cause hepatic cell death directly via the Fas/FasL pathway or indirectly by activating NK cells. 82 , 85 …”

Section: Alteration Of the Liver Immune Microenvironment Promotes The...mentioning

confidence: 99%

“…In addition, activated iNKT cells could cause hepatic cell death directly via the Fas/FasL pathway or indirectly by activating NK cells. 82,85 There is growing evidence from both human patients and animal models suggesting that CD8 + T cells increase in the liver in NASH. [86][87][88] In NASH, CD8 + T cells mainly produce cytokines such as TNF-α, IFN-γ, and IL-10, which drive the activation of HSCs and recruitment of macrophages.…”

Section: Alteration Of the Liver Immune Microenvironment Promotes The...mentioning

confidence: 99%

Pathogenesis from Inflammation to Cancer in NASH-Derived HCC

Yu¹,

Wang²,

Zheng³

et al. 2022

JHC

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the deadliest cancers worldwide. As opposed to the majority of patients with HCC, approximately 20–30% of cases of non-alcoholic steatohepatitis (NASH)-derived HCC develop malignant tumours in the absence of liver cirrhosis. NASH is characterized by metabolic dysregulation, chronic inflammation and cell death in the liver, which provide a favorable setting for the transformation of inflammation into cancer. This review aims to describe the pathogenesis and the underlying mechanism of the transition from inflammation to cancer in NASH.

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“…The narrow definition of NKTs refers to iNKT cells ( Wang and Yin 2015 ), which are also the cell types that we summarize here. After activation, the NKTs release proinflammatory cytokines and interact with other types of innate immune cells ( Nilsson et al, 2020 ). NKTs can not only kill target cells directly but also produce a variety of cytokines, thus playing an important role in liver injury, liver fibrosis, liver regeneration, and the occurrence and development of liver cancer ( Gao et al, 2009 ).…”

Section: Function and Mechanism Of Autophagy And Innate Immunity In L...mentioning

confidence: 99%

Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis

et al. 2022

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Liver fibrosis is a repair process of chronic liver injuries induced by toxic substances, pathogens, and inflammation, which exhibits a feature such as deposition of the extracellular matrix. The initiation and progression of liver fibrosis heavily relies on excessive activation of hepatic stellate cells (HSCs). The activated HSCs express different kinds of chemokine receptors to further promote matrix remodulation. The long-term progression of liver fibrosis will contribute to dysfunction of the liver and ultimately cause hepatocellular carcinoma. The liver also has abundant innate immune cells, including DCs, NK cells, NKT cells, neutrophils, and Kupffer cells, which conduct complicated functions to activation and expansion of HSCs and liver fibrosis. Autophagy is one specific type of cell death, by which the aberrantly expressed protein and damaged organelles are transferred to lysosomes for further degradation, playing a crucial role in cellular homeostasis. Autophagy is also important to innate immune cells in various aspects. The previous studies have shown that dysfunction of autophagy in hepatic immune cells can result in the initiation and progression of inflammation in the liver, directly or indirectly causing activation of HSCs, which ultimately accelerate liver fibrosis. Given the crosstalk between innate immune cells, autophagy, and fibrosis progression is complicated, and the therapeutic options for liver fibrosis are quite limited, the exploration is essential. Herein, we review the previous studies about the influence of autophagy and innate immunity on liver fibrosis and the molecular mechanism to provide novel insight into the prevention and treatment of liver fibrosis.

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NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis

Cited by 15 publications

References 54 publications

Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis

Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis

Pathogenesis from Inflammation to Cancer in NASH-Derived HCC

Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis

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