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https://www.readbyqxmd.com/read/28231294/association-of-neutrophil-lymphocyte-ratio-and-t-lymphocytes-with-the-pathogenesis-and-progression-of-hbv-associated-primary-liver-cancer
#1
Xiaoli Liu, Lingling He, Junyan Han, Lijia Wang, Mengge Li, Yuyong Jiang, Xianbo Wang, Zhiyun Yang
BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a new prognostic predictor for patients with liver cancer. The association of NLR and T lymphocytes with the pathogenesis and progression of liver cancer is poorly understood. METHODS: Seventy-three patients with hepatitis B virus (HBV)-associated primary liver cancer (HBV-PLC), 50 patients with HBV-associated liver cirrhosis (HBV-LC) and 37 patients with chronic HBV infection (CHB) were prospectively enrolled from July 1, 2013 to February 28, 2014 in Beijing Ditan Hospital, Capital Medical University (Beijing, China)...
2017: PloS One
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#2
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#3
Elisabeth Schrumpf, Xiaojun Jiang, Sebastian Zeissig, Marion J Pollheimer, Jarl Andreas Anmarkrud, Corey Tan, Mark A Exley, Tom H Karlsen, Richard S Blumberg, Espen Melum
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d(-/-) mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#4
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28188823/hepatic-stellate-cell-interferes-with-nk-cell-regulation-of-fibrogenesis-via-curcumin-induced-senescence-of-hepatic-stellate-cell
#5
Huanhuan Jin, Yan Jia, Zhen Yao, Jingjing Huang, Meng Hao, Shunyu Yao, Naqi Lian, Feng Zhang, Chenxi Zhang, Xingran Chen, Mianli Bian, Jiangjuan Shao, Li Wu, Anping Chen, Shizhong Zheng
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis...
February 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#6
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28176332/low-dose-interleukin-2-promotes-stat5-phosphorylation-treg-survival-and-ctla-4-dependent-function-in-autoimmune-liver-diseases
#7
Hannah C Jeffery, Louisa E Jeffery, Philipp Lutz, Margaret Corrigan, Gwilym J Webb, Gideon M Hirschfield, David H Adams, Ye Htun Oo
CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and regulatory T cells contribute to the pathogenesis of autoimmune diseases. We recently reported that the hepatic microenvironment is deficient in IL-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate STAT5 phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases...
February 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28143936/ebi3-regulates-the-nk-cell-response-to-mouse-cytomegalovirus-infection
#8
Helle Jensen, Shih-Yu Chen, Lasse Folkersen, Garry P Nolan, Lewis L Lanier
Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3(-/-)) C57BL/6 (B6) mice during MCMV infection...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#9
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104122/role-of-natural-killer-cells-in-the-innate-immune-system-after-intraportal-islet-transplantation-in-mice
#10
Y Saeki, K Ishiyama, N Ishida, Y Tanaka, H Ohdan
BACKGROUND: Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation. METHODS: To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d(-/-) diabetic mice and NK cell-depleted CD1d(-/-) diabetic mice...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28100256/transcriptomic-signatures-differentiate-survival-from-fatal-outcomes-in-humans-infected-with-ebola-virus
#11
Xuan Liu, Emily Speranza, César Muñoz-Fontela, Sam Haldenby, Natasha Y Rickett, Isabel Garcia-Dorival, Yongxiang Fang, Yper Hall, Elsa-Gayle Zekeng, Anja Lüdtke, Dong Xia, Romy Kerber, Ralf Krumkamp, Sophie Duraffour, Daouda Sissoko, John Kenny, Nichola Rockliffe, E Diane Williamson, Thomas R Laws, Magassouba N'Faly, David A Matthews, Stephan Günther, Andrew R Cossins, Armand Sprecher, John H Connor, Miles W Carroll, Julian A Hiscox
BACKGROUND: In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality. RESULTS: The data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection...
January 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28095507/choline-deficiency-causes-colonic-type-ii-natural-killer-t-nkt-cell-loss-and-alleviates-murine-colitis-under-type-i-nkt-cell-deficiency
#12
Shintaro Sagami, Yoshitaka Ueno, Shinji Tanaka, Akira Fujita, Hiroaki Niitsu, Ryohei Hayashi, Hideyuki Hyogo, Takao Hinoi, Yasuhiko Kitadai, Kazuaki Chayama
Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet...
2017: PloS One
https://www.readbyqxmd.com/read/28093522/cutting-edge-human-cd49e-nk-cells-are-tissue-resident-in-the-liver
#13
Han Xian Aw Yeang, Sytse J Piersma, Yiing Lin, Liping Yang, Olga N Malkova, Cathrine Miner, Alexander S Krupnick, William C Chapman, Wayne M Yokoyama
Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e(-) NK cells are tissue resident in the liver...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093337/nk-cell-phenotypic-and-functional-shifts-coincide-with-specific-clinical-phases-in-the-natural-history-of-chronic-hbv-infection
#14
Rik A de Groen, Jun Hou, Gertine W van Oord, Zwier M A Groothuismink, Marieke van der Heide, Robert J de Knegt, André Boonstra
BACKGROUND: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. METHODS: Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells...
January 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-interleukin-23-mediated-protection-against-concanavalin-a-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#15
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ(-/-) ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28073411/-effect-of-umbilical-cord-mesenchymal-stem-cell-transplantation-on-immune-function-and-prognosis-of-patients-with-decompensated-hepatitis-b-cirrhosis
#16
X Q Fang, J F Zhang, H Y Song, Z L Chen, J Dong, X Chen, J J Pan, B Liu, C X Chen
Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on the immune function and prognosis of patients with decompensated hepatitis B cirrhosis. Methods: A total of 65 patients with decompensated hepatitis B cirrhosis were divided into observation group and control group. The patients in the observation group were given intervention (via the proper hepatic artery or the portal vein) and intravenous infusion of 4×10(8) hUCMSCs in two doses, as well as the same basic treatment as in the control group...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28069109/immunomodulatory-effects-of-bone-marrow-mesenchymal-stem-cells-overexpressing-heme-oxygenase-1-protective-effects-on-acute-rejection-following-reduced-size-liver-transplantation-in-a-rat-model
#17
Zhong-Yang Shen, Bin Wu, Tao Liu, Yang Yang, Ming-Li Yin, Wei-Ping Zheng, Bo-Ya Zhang, Hong-Li Song
Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher...
December 26, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28067024/treatment-with-alpha-galactosylceramide-protects-mice-from-early-onset-of-non-alcoholic-steatohepatitis-role-of-intestinal-barrier-function
#18
Anna Janina Engstler, Cathrin Sellmann, Cheng Jun Jin, Annette Brandt, Kathleen Herz, Josephine Priebs, Ina Bergheim
SCOPE: The role of invariant natural killer T cells in the development of non-alcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T cell activator alpha-galactosylceramide (αGalCer) on the development of non-alcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD)-induced NASH. METHODS AND RESULTS: Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 weeks while being treated 3-times weekly with αGalCer (2 μg i...
January 9, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28065449/a-specific-immune-tolerance-toward-offspring-cells-is-to-exist-after-the-mother-lymphocyte-infusion
#19
Haizhou Xing, Shiqin Liu, Xue Chen, Fang Fang, Xueqiang Wu, Ping Zhu
PURPOSE: To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. METHODS: Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10(7) of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected...
December 26, 2016: Immunobiology
https://www.readbyqxmd.com/read/28058287/impact-of-il-27-on-hepatocyte-antiviral-gene-expression-and-function
#20
Narayan Ramamurthy, Sara Boninsegna, Rebecca Adams, Natasha Sahgal, Helen Lockstone, Dilair Baban, Emanuele Marchi, Paul Klenerman
Background: Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines. It is a potent cytokine, with potential antiviral impact, and has been shown to play a role in modulating functions of diverse cell types, including Th1, Th2, and NK and B cells, demonstrating both pro- and anti-inflammatory roles.  In hepatocytes, it is capable of inducing signal transducer and activator of transcription (STAT)1, STAT3 and interferon-stimulated genes. Methods: To address its role in viral hepatitis, the antiviral activity of IL-27 against hepatitis C virus (HCV) and hepatitis B virus (HBV) was tested in vitro using cell-culture-derived infectious HCV (HCVcc) cell culture system and the HepaRG HBV cell culture model...
November 17, 2016: Wellcome Open Res
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