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Nkg2d ligand

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https://www.readbyqxmd.com/read/28322797/transcriptional-activation-of-the-mica-gene-with-an-engineered-crispr-cas9-system
#1
Kazuma Sekiba, Mari Yamagami, Motoyuki Otsuka, Tatsunori Suzuki, Takahiro Kishikawa, Rei Ishibashi, Motoko Ohno, Masaya Sato, Kazuhiko Koike
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28293239/major-histocompatibility-complex-class-i-chain-related-a-mica-molecules-relevance-in-solid-organ-transplantation
#2
REVIEW
Ajay Kumar Baranwal, Narinder K Mehra
An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28283665/il-18-dependent-nkg2d-ligand-upregulation-on-accessory-cells-is-mediated-by-the-pi3k-gsk-3-pathway
#3
Joshua D Brandstadter, Huiyao Chen, Songfu Jiang, Xiaopei Huang, Yiping Yang
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway...
March 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28276625/nkg2d-ligand-rae1%C3%AE%C2%B5-induces-generation-and-enhances-the-inhibitor-function-of-myeloid-derived-suppressor-cells-in-mice
#4
Li Qian, Yang Liu, Shaoqing Wang, Weijuan Gong, Xiaoqin Jia, Lu Liu, Feng Ye, Jingjuan Ding, Yuwei Xu, Yi Fu, Fang Tian
Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D-mediated immune cell activation, such as tumour-derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down-regulate the expression of NKG2D on NK cells and CD8(+) T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b(+) Gr-1(+) myeloid-derived suppressor cell (MDSC) via NKG2D in vitro and in vivo...
March 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28251796/cytotoxicity-of-natural-killer-cells-activated-through-nkg2d-contributes-to-the-development-of-bronchiolitis-obliterans-in-a-murine-heterotopic-tracheal-transplant-model
#5
Toru Kawakami, Koyu Ito, Yasushi Matsuda, Masahumi Noda, Akira Sakurada, Yasushi Hoshikawa, Yoshinori Okada, Kouetsu Ogasawara
Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of NK cells, which have similar functions to CD8(+) T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28245380/-decitabine-enhances-the-sensitivity-of-leukemia-stem-cell-to-allo-nk-cell-mediated-killing
#6
Qian Li, Shan-Shan Wei, Jin-Gao Li, Shao-Xian Chen, Jing Chen, Hui-Ting Huang, Qi Peng, Ping-Fang Xia, Miao-Rong She
OBJECTIVE: To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms. METHODS: LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28237999/the-poly-%C3%AE-d-glutamic-acid-capsule-surrogate-of-bacillus-anthracis-capsule-induces-interferon-gamma-production-in-nk-cells-through-interactions-with-macrophages
#7
Hae-Ri Lee, Jun Ho Jeon, Gi-Eun Rhie
The poly-γ-D-glutamic acid (PGA) capsule, a major virulence factor of Bacillus anthracis, provides protection of the Bacillus from phagocytosis and allows its unimpeded growth in the host. We investigated crosstalk between murine NK cells and macrophages stimulated with PGA capsule of Bacillus licheniformis, a surrogate of B. anthracis capsule. PGA induced interferon-gamma (IFN-γ) production from NK cells cultured with macrophages. This effect was dependent on macrophage-derived IL-12 and cell-cell contact interaction with macrophages through NK cell receptor NKG2D and its ligand RAE-1...
February 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#8
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28223282/induction-of-nkg2d-ligands-on-solid-tumors-requires-tumor-specific-cd8-t-cells-and-histone-acetyltransferases
#9
Jiemiao Hu, Chantale Bernatchez, Liangfang Zhang, Xueqing Xia, Eugenie S Kleinerman, Mien-Chie Hung, Patrick Hwu, Shulin Li
NKG2D-mediated immune surveillance is crucial for inhibiting tumor growth and metastases. Malignant tumor cells often downregulate NKG2D ligands to escape from immune surveillance. High-profile studies have shown that restoring NKG2D ligand expression via genetic engineering inhibits tumor formation and progression. However, no effective in vivo approaches are available to restore these ligands across different types of solid tumors because the classic stress signal-dependent induction of this ligand in vitro is transient and has rarely been duplicated in solid tumors in vivo We found that coadministration of an immune stimulatory signal (IL12) and chemotherapy (doxorubicin) restored the NKG2D ligand Rae-1 in multiple tumor types, including a human tumor model...
February 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28203118/human-u87-glioblastoma-cells-with-stemness-features-display-enhanced-sensitivity-to-natural-killer-cell-cytotoxicity-through-altered-expression-of-nkg2d-ligand
#10
Se-Jeong Oh, Jung-In Yang, Ok Kim, Eun-Jung Ahn, Woo Dae Kang, Jae-Hyuk Lee, Kyung-Sub Moon, Kyung-Hwa Lee, Duck Cho
BACKGROUND: Glioblastoma (GBM) is one of the most lethal tumors with a poor prognosis. Its inevitable recurrence is frequently explained by the presence of cancer stem cells. We aimed to show that human GBM cells with stemness features are more sensitive to natural killer (NK) cells than GBM cells without stemness characteristics. METHODS: Natural killer cell cytotoxicity was measured using flow cytometry in neurosphere-forming U87 GBM cells cultured with neurobasal media (NBE condition) and compared with that in serum-cultured U87 GBM cells (serum condition)...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#11
Alessandra Soriani, Cristiana Borrelli, Biancamaria Ricci, Rosa Molfetta, Alessandra Zingoni, Cinzia Fionda, Silvia Carnevale, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Giuseppe La Regina, Erica Di Cesare, Patrizia Lavia, Romano Silvestri, Rossella Paolini, Marco Cippitelli, Angela Santoni
The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28191644/nk-cell-receptors-nkp46-and-ncr1-control-human-metapneumovirus-infection
#12
Mohammad Diab, Ariella Glasner, Batya Isaacson, Yotam Bar-On, Yaron Drori, Rachel Yamin, Alexandra Duev-Cohen, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Stipan Jonjic, Eran Bacharach, Ofer Mandelboim
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46-activating receptor and its mouse orthologue Ncr1, both members of the natural cytotoxicity receptor (NCR) family, recognized an unknown ligand expressed by HMPV-infected human cells...
February 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28177768/ethanol-dependent-expression-of-the-nkg2d-ligands-mica-b-in-human-cell-lines-and-leukocytes
#13
Maria A Streltsova, Anna V Klinkova, Anastasia A Kuchukova, Andrey Y Kadin, Leonid M Kanevskiy, Elena I Kovalenko
Alcohol consumption affects human immune system, causing a variety of disorders. However, the mechanisms of development of these alterations are not fully understood. We hypothesized that ethanol may influence the expression of MICA and MICB, stress-induced molecules capable to regulate activity of cytotoxic lymphocytes through the interaction with receptor NKG2D, which substantially affects the functionality of cellular immunity. We analyzed effects of ethanol on MICA/B expression in tumor cell lines and human leukocytes...
November 2, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28169232/membrane-bound-versus-soluble-major-histocompatibility-complex-class-i-related-chain-a-and-major-histocompatibility-complex-class-i-related-chain-b-differential-expression-mechanisms-of-tumor-eradication-versus-evasion-and-current-drug-development-strategies
#14
REVIEW
P K Suresh
Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28159927/decreased-expression-of-the-nkg2d-ligand-ulbp4-may-be-an-indicator-of-poor-prognosis-in-patients-with-nasopharyngeal-carcinoma
#15
Yuanji Xu, Lin Zhou, Jingfeng Zong, Yunbin Ye, Gang Chen, Yanping Chen, Xuehong Liao, Qiaojuan Guo, Sufang Qiu, Shaojun Lin, Honglin Chen, Jianji Pan
U16-binding protein 4 (ULBP4), a human ligand for natural killer group 2, member D (NKG2D) receptor on NK cells and subsets of T cells, is thought to activate anticancer immune responses. However, the expression pattern and prognostic effect of ULBP4 in nasopharyngeal carcinoma (NPC) has not been investigated. We first compared ULBP4 expression between archival 15 NPC tissues and 8 normal nasopharynx (NP) tissues using qPCR. Then ULBP4 expression among 111 NPC specimens was validated on immunohistochemical examination...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28128200/the-immunoreceptor-nkg2d-promotes-tumour-growth-in-a-model-of-hepatocellular-carcinoma
#16
Sam Sheppard, Joana Guedes, Anna Mroz, Anastasia-Maria Zavitsanou, Hiromi Kudo, Stephen M Rothery, Panagiotis Angelopoulos, Robert Goldin, Nadia Guerra
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8(+)T cells to the liver and exacerbated pro-inflammatory milieu...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28098874/mica-il-12-a-novel-bifunctional-protein-for-killer-cell-activation
#17
Ashlee Tietje, Xi Yang, Xianzhong Yu, Yanzhang Wei
Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors such as NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce the expression of these ligands, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, such as IL-12. A previous study in our laboratory showed that a fusion protein of the extracellular domain of mouse UL-16 binding protein-like transcript 1 (MULT1E) and mouse interleukin 12 (IL-12) can effectively activate mouse NK cells by in vitro assays and in vivo in animal tumor models...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28089218/nkg2d-signaling-the-immune-subversive-side-of-hdac3
#18
Alicia R Folgueras, Segundo Gonzalez, Alejandro López-Soto
Natural killer (NK) cells are alerted to infected and transformed cells by local upregulation of ligands for the NK-activating receptor NKG2D. In a recent report, Greene et al. unveil a new mechanism that induces the expression of the NKG2D ligand retinoic acid early-inducible (RAE-1) in response to murine cytomegalovirus (MCMV) infection through inhibition of casein kinase 2 (CK2), an activator of the repressor histone deacetylase HDAC3.
March 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28087665/nkg2d-promotes-b1a-cell-development-and-protection-against-bacterial-infection
#19
Maja Lenartić, Vedrana Jelenčić, Biljana Zafirova, Mateja Ožanič, Valentina Marečić, Slaven Jurković, Veronika Sexl, Marina Šantić, Felix M Wensveen, Bojan Polić
NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28055304/synergistic-effect-of-cytokine-induced-killer-cell-with-valproate-inhibits-growth-of-hepatocellular-carcinoma-cell-in-a-mouse-model
#20
Dong Hyeon Lee, Joon Yeul Nam, Young Chang, Hyeki Cho, Seong Hee Kang, Young Youn Cho, EunJu Cho, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
OBJECTIVE: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC...
January 2, 2017: Cancer Biology & Therapy
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