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https://www.readbyqxmd.com/read/28098874/mica-il-12-a-novel-bifunctional-protein-for-killer-cell-activation
#1
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
#2
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.
January 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28087665/nkg2d-promotes-b1a-cell-development-and-protection-against-bacterial-infection
#3
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/28087292/loss-of-cd28-within-cd4-t-cell-subsets-from-cervical-cancer-patients-is-accompanied-by-the-acquisition-of-intracellular-perforin-and-is-further-enhanced-by-nkg2d-expression
#4
Marta Escarra-Senmarti, Miriam Ruth Bueno-Topete, Luis Felipe Jave-Suarez, Eduardo Gomez-Bañuelos, Jorge Gutierrez-Franco, Natali Vega-Magaña, Adriana Aguilar-Lemarroy, Ana Laura Pereira-Suarez, Jesse Haramati, Susana Del Toro-Arreola
CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties...
January 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28076376/increased-natural-killer-cell-activation-in-hiv-infected-immunologic-non-responders-correlates-with-cd4-t-cell-recovery-after-antiretroviral-therapy-and-viral-suppression
#5
Zhenwu Luo, Zhen Li, Lisa Martin, Zhiliang Hu, Hao Wu, Zhuang Wan, Michael Kilby, Sonya L Heath, Lei Huang, Wei Jiang
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders"...
2017: PloS One
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
#6
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 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28031333/t-cells-infiltrating-diseased-liver-express-ligands-for-the-nkg2d-stress-surveillance-system
#7
Wei-Chen Huang, Nicholas J Easom, Xin-Zi Tang, Upkar S Gill, Harsimran Singh, Francis Robertson, Chiwen Chang, John Trowsdale, Brian R Davidson, William M Rosenberg, Giuseppe Fusai, Antoine Toubert, Patrick T Kennedy, Dimitra Peppa, Mala K Maini
NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)-specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28018364/nkg2a-expressing-natural-killer-cells-dominate-the-response-to-autologous-lymphoblastoid-cells-infected-with-epstein-barr-virus
#8
Olivia Hatton, Dara Marie Strauss-Albee, Nancy Q Zhao, Mikel D Haggadone, Judith Shanika Pelpola, Sheri M Krams, Olivia M Martinez, Catherine A Blish
Epstein-Barr virus (EBV) is a human γ-herpesvirus that establishes latency and lifelong infection in host B cells while achieving a balance with the host immune response. When the immune system is perturbed through immunosuppression or immunodeficiency, however, these latently infected B cells can give rise to aggressive B cell lymphomas. Natural killer (NK) cells are regarded as critical in the early immune response to viral infection, but their role in controlling expansion of infected B cells is not understood...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018354/impact-of-the-mica-129met-val-dimorphism-on-nkg2d-mediated-biological-functions-and-disease-risks
#9
REVIEW
Antje Isernhagen, Dörthe Malzahn, Heike Bickeböller, Ralf Dressel
The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8(+) T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011864/combined-immunodeficiency-and-epstein-barr-virus-induced-b-cell-malignancy-in-humans-with-inherited-cd70-deficiency
#10
Hassan Abolhassani, Emily S J Edwards, Aydan Ikinciogullari, Huie Jing, Stephan Borte, Marcus Buggert, Likun Du, Mami Matsuda-Lennikov, Rosa Romano, Rozina Caridha, Sangeeta Bade, Yu Zhang, Juliet Frederiksen, Mingyan Fang, Sevgi Kostel Bal, Sule Haskologlu, Figen Dogu, Nurdan Tacyildiz, Helen F Matthews, Joshua J McElwee, Emma Gostick, David A Price, Umaimainthan Palendira, Asghar Aghamohammadi, Bertrand Boisson, Nima Rezaei, Annika C Karlsson, Michael J Lenardo, Jean-Laurent Casanova, Lennart Hammarström, Stuart G Tangye, Helen C Su, Qiang Pan-Hammarström
In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28004016/peginterferon-alfa-2a-ribavirin-treatment-efficacy-in-chronic-hepatitis-c-patients-is-related-to-natural-killer-group-2d-gene-rs1049174-gc-polymorphism
#11
Abolghasem Asadi-Saghandi, Ali Shams, Gilda Eslami, Seyed Ali Mirghanizadeh, Ebrahim Eskandari-Nasab
Natural killer group 2D (NKG2D), as an activating receptor, plays pivotal role in viral infectious diseases. Several single nucleotide polymorphisms (SNPs) in the NKG2D gene have characterized that the rs1049174G/C SNP of NKG2D is in the spotlight of notice because of its role in activating of human T cells. This study aimed to investigate rs1049174G/C genetic polymorphism in Chronic Hepatitis C (CHC) patients. The study compromised 107 CHC patients with genotype 1a and 1b. All recruited patients were under treatment with Peginterferon Alfa-2a/Ribavirin according to standard protocol...
December 2016: Virusdisease
https://www.readbyqxmd.com/read/27995954/a-functional-polymorphism-in-the-nkg2d-gene-modulates-nk-cell-cytotoxicity-and-is-associated-with-susceptibility-to-human-papilloma-virus-related-cancers
#12
J Luis Espinoza, Viet H Nguyen, Hiroshi Ichimura, Trang T T Pham, Cuong H Nguyen, Thuc V Pham, Mahmoud I Elbadry, Katsuji Yoshioka, Junji Tanaka, Ly Q Trung, Akiyoshi Takami, Shinji Nakao
Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27992381/low-dose-bortezomib-increases-the-expression-of-nkg2d-and-dnam-1-ligands-and-enhances-induced-nk-and-%C3%AE-%C3%AE-t-cell-mediated-lysis-in-multiple-myeloma
#13
Chao Niu, Haofan Jin, Min Li, Shan Zhu, Lei Zhou, Feng Jin, Yulai Zhou, Dongsheng Xu, Jianting Xu, Lianjing Zhao, Shanshan Hao, Wei Li, Jiuwei Cui
Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) or γδ T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and γδ T cells further improves outcomes in MM, and how the treatments should be combined, remain unclear. Herein, we found that low-dose bortezomib did not suppress the viability of induced NK and γδ T cells, but did induce MM cell apoptosis...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27986136/increased-blood-levels-of-nkg2d-cd4-t%C3%A2-cells-in-patients-with-alopecia-areata
#14
Yong Hyun Jang, Jin Kyeong Choi, Yun Hwan Jang, Sun Young Moon, Weon Ju Lee, Seok-Jong Lee, Young-Ae Choi, Sang-Hyun Kim, Do Won Kim
No abstract text is available yet for this article.
January 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27956531/clr-a-a-novel-immune-related-c-type-lectin-like-molecule-exclusively-expressed-by-mouse-gut-epithelium
#15
Emilia Rutkowski, Stefan Leibelt, Christina Born, Miriam E Friede, Stefan Bauer, Sandra Weil, Joachim Koch, Alexander Steinle
The mouse gut epithelium represents a constitutively challenged environment keeping intestinal commensal microbiota at bay and defending against invading enteric pathogens. The complex immunoregulatory network of the epithelial barrier surveillance also involves NK gene complex (NKC)-encoded C-type lectin-like molecules such as NKG2D and Nkrp1 receptors. To our knowledge, in this study, we report the first characterization of the orphan C-type lectin-like molecule Clr-a encoded by the Clec2e gene in the mouse NKC...
December 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27933717/mass-cytometry-analytical-approaches-reveal-cytokine-induced-changes-in-natural-killer-cells
#16
Elena Vendrame, Julia Fukuyama, Dara M Strauss-Albee, Susan Holmes, Catherine A Blish
BACKGROUND: Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here we performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells. METHODS: We used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL- 12/IL-15/IL-18...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933061/ncr1-expression-identifies-canine-natural-killer-cell-subsets-with-phenotypic-similarity-to-human-natural-killer-cells
#17
Jennifer A Foltz, Srinivas S Somanchi, Yanwen Yang, Arianexys Aquino-Lopez, Erin E Bishop, Dean A Lee
Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46), the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#18
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27905484/independent-control-of-natural-killer-cell-responsiveness-and-homeostasis-at-steady-state-by-cd11c-dendritic-cells
#19
Thuy Thanh Luu, Sridharan Ganesan, Arnika Kathleen Wagner, Dhifaf Sarhan, Stephan Meinke, Natalio Garbi, Günter Hämmerling, Evren Alici, Klas Kärre, Benedict J Chambers, Petter Höglund, Nadir Kadri
During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904959/differential-pulmonic-nk-and-nkt-cell-responses-in-schistosoma-japonicum-infected-mice
#20
Hefei Cha, Wenjuan Qin, Quan Yang, Hongyan Xie, Jiale Qu, Mei Wang, Daixiong Chen, Fang Wang, Nuo Dong, Longhua Chen, Jun Huang
Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas...
November 30, 2016: Parasitology Research
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