NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis

Hou, Xin; Zhou, Rongbin; Wei, Haiming; Sun, Rui; Tian, Zhigang

doi:10.1002/hep.22725

Cited by 88 publications

(126 citation statements)

References 47 publications

(57 reference statements)

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“…26,27 However, increasing evidence suggests that NK-cell activation can lead to tissue injury during the inflammatory response. For instance, NK cells activated by poly I:C and D-galactosamine injection can cause overproduction of IFN-c, which causes damage to hepatocytes, 28 and NK cells are also involved in the lung immune injury at the early stage of respiratory syncytial virus infection. 29 Inspired by the findings in our study, we may control the extent of NK-cell activation using genetic methods to regulate the expression of activating and inhibitory receptors on NK cells, which may provide a therapy to improve the host's immune response or to control disease caused by excessive NK-cell immune response.…”

Section: Discussionmentioning

confidence: 99%

Lung natural killer cells in mice: phenotype and response to respiratory infection

Wang

Zheng

et al. 2012

Immunology

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SummaryNatural killer (NK) cells have a specialized function in peripheral organs, which is determined by the organ-specific niches. We have attempted to explore whether lung NK cells display a particular phenotype according to their function in the unique pulmonary environment in health or during respiratory infection in mice. In healthy mice, higher frequencies of NK cells among lymphocytes were detected in the lung than in other tissues (lymph node, bone marrow, spleen, blood and liver), and lung NK cells maintained a more mature phenotype, implying that lung NK cells were critical for the pulmonary immune response. However, lung NK cells expressed higher levels of inhibitory receptors and lower levels of activating receptors, migration/adhesion-associated molecules and co-stimulatory molecules than splenic NK cells, implying that lung NK cells were quiescent, and the activation of lung NK cells was tightly regulated by the pulmonary environment in health. During respiratory infection, lung NK cells could be activated and express functional molecules (CD107a and interferon-c) to take part in the response to infection quickly. These results suggested that the unique pulmonary environment promotes the development of NK cells with a lung-specific phenotype.

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Section: Discussionmentioning

confidence: 99%

Lung natural killer cells in mice: phenotype and response to respiratory infection

Wang

Zheng

et al. 2012

Immunology

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“…CD4 + T cells were separated by positive magnetic cell sorting using an anti-CD4 mAb according to the manufacturer's instructions (Miltenyi Biotec). KC isolations were performed as previously described (35).…”

Section: Methodsmentioning

confidence: 99%

Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice

Yin

Sun

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-carrier mouse model, and found that these mice exhibited an antigen-specific tolerance toward peripheral HBsAg vaccination, showing unenlarged draining lymph node (DLN), lower number of germinal centers (GC), and inactivation of GC B cells and follicular T helper (Tfh) cells. Both in vivo and in vitro immune responses toward HBsAg were suppressed by mononuclear cells from HBV-carrier mice, which were CD4 + Foxp3 − type 1 regulatory T (Tr1)-like cells producing IL-10. Using recipient Rag1 −/− mice, hepatic Tr1-like cells from day 7 of HBV-persistent mice acquired the ability to inhibit anti-HBV immunity 3 d earlier than splenic Tr1-like cells, implying that hepatic Tr1-like cells were generated before those in spleen. Kupffer cell depletion or IL-10 deficiency led to impairment of Tr1-like cell generation, along with breaking HBV persistence. The purified EGFP + CD4 + T cells (containing Tr1-like cells) from HBV-carrier mice trafficked in higher numbers to DLN in recipient mice after HBsAg vaccination, and subsequently inactivated both Tfh cells and GC B cells via secreting IL-10, resulting in impaired GC formation and anti-HB antibody production. Thus, our results indicate Tr1-like cells migrate from the liver to the DLN and inhibit peripheral anti-HBV immunity by negatively regulating GC B cells and Tfh cells.peripheral tolerance | unresponsive

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“…Nevertheless, this seems of great clinical importance as NK and NKT cells have been reproducibly shown to be functionally relevant in acute liver disease models. [18][19][20] Therefore, we here analyze the specific role of CXCR3 and its impact on NK and NKT cell recruitment during the early phases of toxic liver damage.…”

Section: Cxcr3 In Acute Toxic Liver Injurymentioning

confidence: 99%

The chemokine receptor CXCR3 limits injury after acute toxic liver damage

Zaldivar

Berres

Sahin

et al. 2012

Laboratory Investigation

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Although acute liver failure is a rare disease, its presence is associated with high morbidity and mortality in affected patients. While a contribution of the immune system to the outcome of toxic liver failure is anticipated, functionally relevant immune cell receptors for liver cell damage need to be better defined. We here investigate the relevance of the chemokine receptor CXCR3, which is important for hepatic immune cell infiltration, in a model of experimental acute liver failure. Liver injury was induced by a single intraperitoneal injection of carbon tetrachloride (CCl 4 ) in CXCR3 À/À , CCR1 À/À , CCR5 À/À and wild-type mice. In this model, CXCR3 À/À mice displayed augmented liver damage compared with all other mouse strains as assessed by liver histology and serum transaminases 24 and 72 h after injury. Phenotypically, CXCR3 À/À mice had significantly reduced intrahepatic NK and NKT cells after injury at all investigated time points (all Po0.05), but strongly elevated expression levels of IL1-b, TNF-a and IFN-g. In line with a functional role of innate immune cells, wildtype mice depleted for NK cells with an anti-ASIALO GM1 antibody before liver injury also displayed increased liver injury after CCl 4 challenge. CXCR3 À/À and NK cell-depleted mice show reduced apoptotic liver cells (TUNEL assay), but more necrotic hepatocytes. Functionally, the augmented liver cell necrosis in CXCR3 À/À and NK cell-depleted mice was associated with increased expression of high mobility group 1 (HMGB1) protein and a consecutive enhanced infiltration of neutrophils into the liver. In conclusion, the results demonstrate a primarily unexpected beneficial role of CXCR3 in acute toxic liver injury. These findings should be taken into account when planning trials with CXCR3 antagonists. Although liver failure is a quite rare clinical condition, its appearance is associated with high mortality and morbidity in affected individuals. The main identifiable causes of acute liver failure are drugs, toxins and viral infections. 1 From a pathophysiological point of view, acute toxic liver failure results from a massive necrosis of hepatocytes that provokes a strong inflammatory immune response within the liver. 2 Upon activation, liver resident and infiltrating immune cells (including T cells, NK cells and NKT cells) secrete diverse proinflammatory chemokines and cytokines, including interferon (IFN)-g 3,4 which perpetuate liver cell damage. IFN-g in turn strongly activates the transcription of the chemokines CXCL9, CXCL10 and CXCL11. 5 The canonical receptor for all three chemokines is CXCR3, 6 which is expressed on various cell sub-populations within the liver, including liver endothelial cells, stellate cells, T cells, NK cells 7 and NKT cells. 8 The interaction between these three chemokines and their receptor mediates the attachment of these immune cells to endothelial cells 9 and thus appears to be crucial for the recruitment of T, NK and NKT cells into the liver. 10,11 Activated hepatic NKT cells by themselves also secrete la...

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NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis

Cited by 88 publications

References 47 publications

Lung natural killer cells in mice: phenotype and response to respiratory infection

Lung natural killer cells in mice: phenotype and response to respiratory infection

Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice

The chemokine receptor CXCR3 limits injury after acute toxic liver damage

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