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NKG2D

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https://www.readbyqxmd.com/read/29691386/toll-like-receptors-mediated-pathways-activate-inflammatory-responses-in-the-esophageal-mucosa-of-adult-eosinophilic-esophagitis
#1
Ángel Arias, María Vicario, David Bernardo, José M Olalla, Marina Fortea, Ana Montalban-Arques, Pilar Martínez-Fernández, Ana M González-Castro, Teresa Mota-Huertas, Laura Arias-González, Alfredo J Lucendo
OBJECTIVES: Esophageal microbiota and regulation of adaptive immunity are increasingly being investigated in eosinophilic esophagitis (EoE). Toll-like receptors (TLRs) play a central role in the initiation and maintenance of innate immune activity. Our objective was to characterize the esophageal and duodenal innate immune response in EoE and its modulation by dietary therapy. METHODS: Esophageal and duodenal biopsy samples were collected from 10 adults with untreated EoE, before and after effective treatment with a six-food elimination diet (SFED), and 10 controls with normal esophagus...
April 25, 2018: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/29690909/targeting-chemotherapy-resistant-leukemia-by-combining-dnt-cellular-therapy-with-conventional-chemotherapy
#2
Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D Minden, Li Zhang
BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy...
April 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29683892/implication-of-highly-cytotoxic-natural-killer-cells-for-esophageal-squamous-cell-carcinoma-treatment
#3
Kee Siang Lim, Kosaku Mimura, Ley-Fang Kua, Kensuke Shiraishi, Koji Kono
Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29680372/inkt-cells-ameliorate-human-autoimmunity-lessons-from-alopecia-areata
#4
Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G Schrum, Ralf Paus, Amos Gilhar
Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10...
April 18, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29679656/pd-1-blocks-lytic-granule-polarization-with-concomitant-impairment-of-integrin-outside-in-signaling-in-natural-killer-cell-immunological-synapse
#5
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29679490/increased-nk-cell-subsets-with-inhibitory-cytokines-and-inhibitory-surface-receptors-in-patients-with-recurrent-miscarriage-and-decreased-or-normal-subsets-in-kidney-transplant-recipients-late-post-transplant
#6
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Naruemol Ekpoom, Gerhard Opelz, Volker Daniel
BACKGROUND: Patients with recurrent miscarriage (RM) show up-regulated cytotoxic NK cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). METHODS: NK, NKT and T cell subsets were analyzed in the peripheral blood of 31 RM, 14 female ESRD and 9 female TX patients as well as 21 female HC using eight-color fluorescence flow cytometry...
April 21, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29662484/nkg2d-and-its-ligands-one-for-all-all-for-one
#7
REVIEW
Alessandra Zingoni, Rosa Molfetta, Cinzia Fionda, Alessandra Soriani, Rossella Paolini, Marco Cippitelli, Cristina Cerboni, Angela Santoni
The activating receptor NKG2D is peculiar in its capability to bind to numerous and highly diversified MHC class I-like self-molecules. These ligands are poorly expressed on normal cells but can be induced on damaged, transformed or infected cells, with the final NKG2D ligand expression resulting from multiple levels of regulation. Although redundant molecular mechanisms can converge in the regulation of all NKG2D ligands, different stimuli can induce specific cellular responses, leading to the expression of one or few ligands...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29651291/cutting-an-nkg2d-ligand-short-cellular-processing-of-the-peculiar-human-nkg2d-ligand-ulbp4
#8
Tobias Zöller, Mareike Wittenbrink, Meike Hoffmeister, Alexander Steinle
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous "self cells" by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1-6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D-NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29650045/characterization-of-the-interaction-between-human-decidua-parietalis-mesenchymal-stem-stromal-cells-and-natural-killer-cells
#9
M H Abumaree, E Bahattab, A Alsadoun, A Al Dosaimani, F M Abomaray, T Khatlani, B Kalionis, M F El-Muzaini, A O Alawad, A S AlAskar
BACKGROUND: Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities. METHODS: DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood...
April 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29643123/intragenic-transcriptional-interference-regulates-the-human-immune-ligand-mica
#10
Da Lin, Thomas K Hiron, Christopher A O'Callaghan
Many human genes have tandem promoters driving overlapping transcription, but the value of this distributed promoter configuration is generally unclear. Here we show that MICA , a gene encoding a ligand for the activating immune receptor NKG2D, contains a conserved upstream promoter that expresses a noncoding transcript. Transcription from the upstream promoter represses the downstream standard promoter activity in cis through transcriptional interference. The effect of transcriptional interference depends on the strength of transcription from the upstream promoter and can be described quantitatively by a simple reciprocal repressor function...
April 11, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29625837/hbsag-stimulates-nkg2d-receptor-expression-on-natural-killer-cells-and-inhibits-hepatitis-c-virus-replication
#11
Xiao-Xiao Wang, Xiao-Ben Pan, Jin-Chao Han, Xu Cong, Qian Jin, Xiang-Sha Kong, Lai Wei, Bo Feng
BACKGROUND: Higher hepatitis B surface antigen (HBsAg) facilitates hepatitis C virus (HCV) clearance in patients with hepatitis B virus (HBV)/HCV co-infection. We investigated the effect of exogenous HBsAg on the inhibition of HCV replication mediated by natural killer (NK) cells. METHODS: After isolated from peripheral blood of 42 chronic hepatitis B (CHB) patients and 16 healthy individuals, NK cells were co-cultured with HCV-infected Huh7 cells, respectively, with or without HBsAg...
March 26, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/29625833/celyad-s-novel-car-t-cell-therapy-for-solid-malignancies
#12
Caroline Lonez, Alain Hendlisz, Leila Shaza, Philippe Aftimos, Michaël Vouche, Vincent Donckier, Jean-Pascal H Machiels, Marc Van Den Eynde, Jean-Luc Canon, Javier Carrasco, Kunle Odunsi, Solmaz Sahebjam, Sylvie Rottey, Nathalie Braun, Bikash Verma, David E Gilham, Frédéric F Lehmann
Celyad recently initiated several clinical trials with the CYAD-01 product, a natural killer group 2D (NKG2D)-based chimeric antigen receptor (CAR), in both solid and hematologic tumor types. This review discusses the unique properties of CYAD-01, expecting to provide a new paradigm to fight against solid tumors.
April 3, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29602283/korean-mistletoe-lectin-enhances-natural-killer-cell-cytotoxicity-via-upregulation-of-perforin-expression
#13
Younghoon Kim, Inbo Kim, Choon-Ho Park, Jong Bae Kim
BACKGROUND: Natural killer (NK) cells are crucial components of the innate immune system, providing the first line of defense against pathogens. In a previous study, we demonstrated prophylactic activity of water extract of Korean mistletoe (Viscum album coloratum) on tumor metastasis. However, the leading compound from water extract of Korean mistletoe was not clearly addressed. OBJECTIVE: The purpose of this research was mainly focused on addressing the effect of Korean mistletoe lectin (KMLC) on NK cell cytotoxicity, and the ability of cytokine secretion as well as its signal transduction, mitogen-activated protein kinase (MAPK) pathway...
March 31, 2018: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/29599246/antibody-mediated-inhibition-of-mica-and-micb-shedding-promotes-nk-cell-driven-tumor-immunity
#14
Lucas Ferrari de Andrade, Rong En Tay, Deng Pan, Adrienne M Luoma, Yoshinaga Ito, Soumya Badrinath, Daphne Tsoucas, Bettina Franz, Kenneth F May, Christopher J Harvey, Sebastian Kobold, Jason W Pyrdol, Charles Yoon, Guo-Cheng Yuan, F Stephen Hodi, Glenn Dranoff, Kai W Wucherpfennig
MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model...
March 30, 2018: Science
https://www.readbyqxmd.com/read/29582167/amniotic-membrane-extract-differentially-regulates-human-peripheral-blood-t-cell-subsets-monocyte-subpopulations-and-myeloid-dendritic-cells
#15
Paula Laranjeira, Marta Duque, Martin Vojtek, Maria J Inácio, Isabel Silva, Ana C Mamede, Mafalda Laranjo, Susana Pedreiro, Maria J Carvalho, Paulo Moura, Ana M Abrantes, Cláudio J Maia, Pedro Domingues, Rosário Domingues, António Martinho, Maria F Botelho, Hélder Trindade, Artur Paiva
The discovery of the immunoregulatory potential of human amniotic membrane (hAM) propelled several studies focusing on its application for the treatment of immunological disorders. However, there is little information regarding the effects of hAM on distinct activation and differentiation stages of immune cells. Here, we aim to investigate the effect of human amniotic membrane extract (hAME) on the pattern of cytokine production by T cells, monocytes and myeloid dendritic cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from eight healthy individuals were stimulated in vitro in the presence or absence of hAME...
March 26, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29581297/inhibition-of-enhancer-of-zeste-homolog-2-ezh2-induces-natural-killer-cell-mediated-eradication-of-hepatocellular-carcinoma-cells
#16
Suresh Bugide, Michael R Green, Narendra Wajapeyee
Natural killer (NK) cell-mediated tumor cell eradication could inhibit tumor initiation and progression. However, the factors that regulate NK cell-mediated cancer cell eradication remain unclear. We determined that hepatocellular carcinoma (HCC) cells exhibit transcriptional down-regulation of NK group 2D (NKG2D) ligands and are largely resistant to NK cell-mediated eradication. Because the down-regulation of NKG2D ligands occurred at the transcriptional level, we tested 32 chemical inhibitors of epigenetic regulators for their ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor of NKG2D ligands...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29580037/analysis-of-the-expression-of-surface-receptors-on-nk-cells-and-nkg2d-on-immunocytes-in-peripheral-blood-of-patients-with-nasopharyngeal-carcinoma
#17
Yuanji Xu, Rui Zhou, Chuanzhong Huang, Mingwei Zhang, Jieyu Li, Jingfeng Zong, Sufang Qiu, Shaojun Lin, Honglin Chen, Yunbin Ye, Jianji Pan
Background: The aberrant expression of surface receptors on immunocytes may represent potential markers of tumor escape for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the expression of representative receptors on natural killer (NK) cells and NK group 2, member D (NKG2D) on immunocytes in the peripheral blood of patients with NPC. Methods: Patients (n = 64) with NPC prior to initiation of treatment were defined as the study group. Healthy volunteers (n = 31) served as the control group...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29568297/nkg2d-a-master-regulator-of-immune-cell-responsiveness
#18
REVIEW
Felix M Wensveen, Vedrana Jelenčić, Bojan Polić
NKG2D is an activating receptor that is mostly expressed on cells of the cytotoxic arm of the immune system. Ligands of NKG2D are normally of low abundance, but can be induced in virtually any cell in response to stressors, such as infection and oncogenic transformation. Engagement of NKG2D stimulates the production of cytokines and cytotoxic molecules and traditionally this receptor is, therefore, viewed as a molecule that mediates direct responses against cellular threats. However, accumulating evidence indicates that this classical view is too narrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29568203/role-of-relevant-immune-modulators-and-cytokines-in-hepatocellular-carcinoma-and-premalignant-hepatic-lesions
#19
Abdel-Rahman N Zekri, Somaya El Deeb, Abeer A Bahnassy, Abeer M Badr, Mona S Abdellateif, Gamal Esmat, Hosny Salama, Marwa Mohanad, Ahmed Esam El-Dien, Shimaa Rabah, Assmaa Abd Elkader
AIM: To assess the levels of different immune modulators in patients with hepatocellular carcinoma (HCC), in relation to other hepatic diseases. METHODS: Eighty-eight patients were included in the current study and represented patients with HCC (20), liver cirrhosis (28) and chronic hepatitis (CH; 25), and normal controls (NC; 15). Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells (mDCs; CD1c and CD40), mature inactive myeloid cells (CD1c and HLA), active plasmacytoid cells (pDCs; CD303 and CD40), mature inactive pDCs (CD30 and HLA), active natural killer (NK) cells (CD56 and CD161), active NK cells (CD56 and CD314) and inactive NK cells (CD56 and CD158) was done by flow cytometry...
March 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29562476/-mechanism-of-nkg2d-ligands-mediated-immune-escape-of-adriamycin-resistant-leukemia-k562-a02-cells
#20
Z X Jia, X H Cai, R Xiao, X W Zhang, X Wu, W M Han, M Zhou, Z C Zhu, X Z Lu
No abstract text is available yet for this article.
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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