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https://www.readbyqxmd.com/read/29908921/il-15-and-ifn-%C3%AE-signal-through-the-erk-pathway-to-inhibit-hcv-replication-independent-of-type-i-ifn-signaling
#1
Fatemeh Vahedi, Amanda J Lee, Susan E Collins, Marianne V Chew, Evan Lusty, Branson Chen, Anisha Dubey, Carl D Richards, Jordan J Feld, Rodney S Russell, Karen L Mossman, Ali A Ashkar
Despite effective new treatments for Hepatitis C virus (HCV) infection, development of drug resistance, safety concerns and cost are remaining challenges. More importantly, there is no vaccine available against hepatitis C infection. Recent data suggest that there is a strong correlation between spontaneous HCV clearance and human NK cell function, particularly IFN-γ production. Further, IL-15 has innate antiviral activity and is also one of the main factors that activates NK cells to produce IFN-γ. To examine whether IL-15 and IFN-γ have direct antiviral activity against HCV, Huh7...
June 13, 2018: Cytokine
https://www.readbyqxmd.com/read/29907809/killer-cell-immunoglobulin-like-receptor-ligand-mismatching-and-outcome-after-haploidentical-transplantation-with-post-transplant-cyclophosphamide
#2
Avichai Shimoni, Myriam Labopin, Francesca Lorentino, Maria Teresa Van Lint, Yener Koc, Zafer Gülbas, Johanna Tischer, Benedetto Bruno, Didier Blaise, Pietro Pioltelli, Boris Afanasyev, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Haploidentical stem cell transplantation with T cell-replete grafts and post-transplant cyclophosphamide (PTCy) is increasingly used with encouraging outcome. Natural killer (NK) cell alloreactivity, predicted by missing killer cell immunoglobulin-like receptor (KIR) ligands in the recipient that are present in their donor improves outcome of T cell-depleted haploidentical transplants. We explored the role of KIR ligand mismatching in 444 acute leukemia patients after T cell-replete transplants with PTCy. Thirty-seven percent of all patients had KIR ligand mismatching...
June 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29904904/ilixadencel-an-allogeneic-cell-based-anticancer-immune-primer-for-intratumoral-administration
#3
Alex Karlsson-Parra, Juliana Kovacka, Emilia Heimann, Margareth Jorvid, Sijme Zeilemaker, Sharon Longhurst, Peter Suenaert
Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8+ T cells without the need for tumor antigen characterization. The prevailing view is that these cross-presenting DCs have to be directly activated by pathogen-associated molecular patterns (PAMPS), including Toll-like receptor ligands or live microbial agents like oncolytic viruses. Emerging data are however challenging this view, indicating that the cross-presenting machinery in DCs is suboptimally activated by direct PAMP recognition, and that endogenous inflammatory factors are the main drivers of DC-mediated cross-presentation within the tumor...
June 14, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29904386/costimulatory-function-of-cd58-cd2-interaction-in-adaptive-humoral-immunity-in-a-zebrafish-model
#4
Tong Shao, Wei Shi, Jia-Yu Zheng, Xiao-Xiao Xu, Ai-Fu Lin, Li-Xin Xiang, Jian-Zhong Shao
CD58 and CD2 have long been known as a pair of reciprocal adhesion molecules involved in the immune modulations of CD8+ T and NK-mediated cellular immunity in humans and several other mammals. However, the functional roles of CD58 and CD2 in CD4+ T-mediated adaptive humoral immunity remain poorly defined. Moreover, the current functional observations of CD58 and CD2 were mainly acquired from in vitro assays, and in vivo investigation is greatly limited due to the absence of a Cd58 homology in murine models...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29904050/amino-acid-dependent-cmyc-expression-is-essential-for-nk-cell-metabolic-and-functional-responses-in-mice
#5
Róisín M Loftus, Nadine Assmann, Nidhi Kedia-Mehta, Katie L O'Brien, Arianne Garcia, Conor Gillespie, Jens L Hukelmann, Peter J Oefner, Angus I Lamond, Clair M Gardiner, Katja Dettmer, Doreen A Cantrell, Linda V Sinclair, David K Finlay
Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked...
June 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29901635/rapamycin-treatment-for-amyotrophic-lateral-sclerosis-protocol-for-a-phase-ii-randomized-double-blind-placebo-controlled-multicenter-clinical-trial-rap-als-trial
#6
Jessica Mandrioli, Roberto D'Amico, Elisabetta Zucchi, Annalisa Gessani, Nicola Fini, Antonio Fasano, Claudia Caponnetto, Adriano Chiò, Eleonora Dalla Bella, Christian Lunetta, Letizia Mazzini, Kalliopi Marinou, Gianni Sorarù, Sara de Biasi, Domenico Lo Tartaro, Marcello Pinti, Andrea Cossarizza
INTRODUCTION: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29899194/heterozygous-deletion-of-lrp5-gene-in-mice-alters-profile-of-immune-cells-and-modulates-differentiation-of-osteoblasts
#7
Lisha Li, Yan Wang, Na Zhang, Yang Zhang, Jing Lin, Xuemin Qiu, Yuyan Gui, Feifei Wang, Dajin Li, Ling Wang
Skeletal homeostasis is dynamically influenced by the immune system. Low density lipoprotein receptor-related protein-5 (LRP5) is a co-receptor of the Wnt signaling pathway, which modulates bone metabolism in humans and mice. Immune disorders can lead to abnormal bone metabolism. It is unclear whether and how LRP5 alters the balance of the immune system to modulate bone homeostasis. In this study, we used primary osteoblast to detect the differentiation of osteoblasts in vitro, the immune cells of spleen and bone marrow of 6-month old LRP5 heterozygote (HZ) and wild-type (WT) mice were analyzed by Flow cytometry...
June 14, 2018: Bioscience Trends
https://www.readbyqxmd.com/read/29898788/immunomodulatory-activities-of-pixatimod-emerging-nonclinical-and-clinical-data-and-its-potential-utility-in-combination-with-pd-1-inhibitors
#8
Edward Hammond, Nicole M Haynes, Carleen Cullinane, Todd V Brennan, Darryn Bampton, Paul Handley, Tomislav Karoli, Fleur Lanksheer, Liwen Lin, Yiping Yang, Keith Dredge
BACKGROUND: Pixatimod (PG545) is a novel clinical-stage immunomodulatory agent capable of inhibiting the infiltration of tumor-associated macrophages (TAMs) yet also stimulate dendritic cells (DCs), leading to activation of natural killer (NK) cells. Preclinically, pixatimod inhibits heparanase (HPSE) which may be associated with its inhibitory effect on TAMs whereas its immunostimulatory activity on DCs is through the MyD88-dependent TLR9 pathway. Pixatimod recently completed a Phase Ia monotherapy trial in advanced cancer patients...
June 14, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29897952/hepatic-irradiation-persistently-eliminates-liver-resident-nk-cells
#9
Ryosuke Nakano, Masahiro Ohira, Takuya Yano, Yuki Imaoka, Yuka Tanaka, Hideki Ohdan
Hepatic irradiation for the treatment of hepatobiliary malignancies often indirectly damages liver tissue and promotes the development of liver fibrosis. However, little is known concerning the effects of hepatic irradiation on the liver immune system, including natural killer (NK) cells. The aim of this study was therefore to investigate how hepatic irradiation influences the functions and characteristics of liver resident NK cells. An established murine hepatic irradiation model was used to examine the specific effects of hepatic irradiation on immune cell populations and metastasis...
2018: PloS One
https://www.readbyqxmd.com/read/29896680/ebv-in-t-nk-cell-tumorigenesis
#10
Hiroshi Kimura
Epstein-Barr virus (EBV), which is associated with B-cell proliferative disorders, also transforms T- or natural killer (NK)-lineage cells and has been connected with various T- or NK (T/NK)-cell malignancies, such as extranodal NK/T-cell lymphoma-nasal type and aggressive NK-cell leukemia. Chronic active EBV (CAEBV) disease , which occurs most often in children and young adults in East Asia, is an EBV-associated T-/NK-cell lymphoproliferative disease. Patients with CAEBV often progress to overt lymphoma or leukemia over a long-term clinical course...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29895693/distinct-human-circulating-nkp30-fc%C3%AE%C2%B5ri%C3%AE-cd8-t-cell-population-exhibiting-high-natural-killer-like-antitumor-potential
#11
Margareta P Correia, Ana Stojanovic, Katharina Bauer, Dilafruz Juraeva, Lars-Oliver Tykocinski, Hanns-Martin Lorenz, Benedikt Brors, Adelheid Cerwenka
CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells...
June 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29894746/a-novel-ebola-virus-antibody-dependent-cell-mediated-cytotoxicity-ebola-adcc-assay
#12
Karnail Singh, Bishal Marasini, Xuemin Chen, Paul Spearman
Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potential mechanism through which anti-Ebola antibodies may mediate protection. We developed a robust Ebola-specific ADCC assay for use in ongoing trials of Ebola vaccines. Stable cell lines for inducible Zaire ebolavirus glycoprotein (EBOV GP) expression were developed to provide a uniform source of target cells in the assay, and were combined with an existing human natural killer (NK) cell line as the effector cell...
June 9, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29892299/iq-domain-containing-gtpase-activating-protein-1-regulates-cytoskeletal-reorganization-and-facilitates-nkg2d-mediated-mechanistic-target-of-rapamycin-complex-1-activation-and-cytokine-gene-translation-in-natural-killer-cells
#13
Alex M Abel, Aradhana A Tiwari, Zachary J Gerbec, Jason R Siebert, Chao Yang, Nathan J Schloemer, Kate J Dixon, Monica S Thakar, Subramaniam Malarkannan
Natural killer (NK) cells are innate lymphocytes that play essential roles in mediating antitumor immunity. NK cells respond to various inflammatory stimuli including cytokines and stress-induced cellular ligands which activate germline-encoded activation receptors (NKRs), such as NKG2D. The signaling molecules activated downstream of NKRs are well defined; however, the mechanisms that regulate these pathways are not fully understood. IQ domain-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29891204/stereotactic-ablative-radiation-therapy-induces-systemic-differences-in-peripheral-blood-immunophenotype-dependent-on-irradiated-site
#14
Heather M McGee, Megan E Daly, Sohelia Azghadi, Susan L Stewart, Leslie Oesterich, Jeffrey Schlom, Renee Donahue, Jonathan D Schoenfeld, Qian Chen, Shyam Rao, Ruben C Fragoso, Richard K Valicenti, Robert J Canter, Emmanual M Maverakis, William J Murphy, Karen Kelly, Arta M Monjazeb
PURPOSE: Despite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune response to SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs. METHODS AND MATERIALS: Patients receiving SAR to any organ underwent prospective blood banking before and 1 to 2 weeks after SAR...
April 22, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29888292/suppression-of-th17-cell-response-in-the-alleviation-of-dextran-sulfate-sodium-induced-colitis-by-ganoderma-lucidum-polysaccharides
#15
Bing Wei, Ran Zhang, Jingbo Zhai, Junfeng Zhu, Fangli Yang, Dan Yue, Xiaoyi Liu, Changlong Lu, Xun Sun
Background: Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. Methods: The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29886157/regulation-of-epithelial-injury-and-bile-duct-obstruction-by-nlrp3-and-il-1r1-in-experimental-biliary-atresia
#16
Li Yang, Tatsuki Mizuochi, Pranavkumar Shivakumar, Reena Mourya, Zhenhua Luo, Sridevi Gutta, Jorge A Bezerra
BACKGROUND & AIMS: Biliary atresia (BA) results from a neonatal inflammatory and fibrosing obstruction of bile ducts of unknown etiology. Although the innate immune system has been linked to virus-induced mechanism of disease, the role of the inflammasome-mediated epithelial injury remains largely undefined. Here, we hypothesized that disruption of the inflammasome suppresses the neonatal proinflammatory response and prevents experimental BA. METHODS: We determined the expression of key inflammasome-related genes in livers from infants at diagnosis of BA and in extrahepatic bile ducts (EHBDs) of neonatal mice after infection with rotavirus (RRV) immediately after birth...
June 7, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29886054/differential-activation-of-intraepithelial-lymphocyte-natural-killer-cells-in-chickens-infected-with-very-virulent-and-vaccine-strains-of-infectious-bursal-disease-virus
#17
Mohammad Zareian Jahromi, Muhammad Bashir Bello, Mostafa Abdolmaleki, Swee Keong Yeap, Mohd Hair-Bejo, Abdul Rahman Omar
To gain insights into the role of CD3- /28.4+ intraepithelial lymphocytes-natural killer (CD3- /28.4+ IEL-NK) cells during infectious bursal disease virus (IBDV) infection, characterization of the cells was performed following infection with different strains of the virus. In vitro treatment with IL-18 or ionomycin/PMA successfully stimulated and activated the cells via a significant increase in the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin. Similarly, chickens infected with the vaccine strain of IBDV also up-regulated the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin in CD3- /28...
June 7, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29885835/hif-1%C3%AE-induces-immune-escape-of-prostate-cancer-by-regulating-ncr1-nkp46-signaling-through-mir-224
#18
Chao-Hao Chen, Shao-Xun Li, Lu-Xia Xiang, Hai-Qi Mu, Shuai-Bin Wang, Kai-Yuan Yu
BACKGROUND: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1α. METHODS: MiR-224 expression in lymphocytes and HIF-1α protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46+ NK cells was detected with flow cytometry. The IFN-γ level was examined by enzyme linked immunosorbent assay (ELISA)...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29882143/natural-killer-nk-cell-assays-in-immunotoxicity-testing
#19
Qing Li
It is well known that natural killer (NK) cells are involved in defense against viruses and some tumors. NK cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes, and granulysin. It is increasingly important to evaluate NK cell function in immunotoxicity testing. NK cell function can be evaluated by determining cytolytic activity against target tumor cells by the 51 Cr-release assay and also by determining the number of NK cells in peripheral blood in humans and in the spleen in animals using flow cytometry...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29876351/industrializing-autologous-adoptive-immunotherapies-manufacturing-advances-and-challenges
#20
REVIEW
Rohin K Iyer, Paul A Bowles, Howard Kim, Aaron Dulgar-Tulloch
Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials...
2018: Frontiers in Medicine
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