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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
#1
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 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/27982126/interleukin-12-bypasses-common-gamma-chain-signalling-in-emergency-natural-killer-cell-lymphopoiesis
#2
Isabel Ohs, Maries van den Broek, Kathrin Nussbaum, Christian Münz, Sebastian J Arnold, Sergio A Quezada, Sonia Tugues, Burkhard Becher
Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122(+)CD49b(+) cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM)...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27933717/mass-cytometry-analytical-approaches-reveal-cytokine-induced-changes-in-natural-killer-cells
#3
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
#4
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/27924822/il-21-dependent-expansion-of-memory-like-nk-cells-enhances-protective-immune-responses-against-mycobacterium-tuberculosis
#5
S Venkatasubramanian, S Cheekatla, P Paidipally, D Tripathi, E Welch, A R Tvinnereim, R Nurieva, R Vankayalapati
Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27919749/in-vitro-vla-4-blockade-results-in-an-impaired-nk-cell-mediated-immune-surveillance-against-melanoma
#6
Ilaria Gandoglia, Federico Ivaldi, Paolo Carrega, Eric Armentani, Guido Ferlazzo, Gianluigi Mancardi, Nicole Kerlero de Rosbo, Antonio Uccelli, Alice Laroni
Natalizumab (NTZ) is a monoclonal antibody targeting the α4β1 integrin (CD49d/CD29), very late antigen-4 (VLA-4), which is approved for treatment of relapsing-remitting multiple sclerosis (RR-MS). A possible association between NTZ treatment and a higher risk of melanoma is under debate. Natural Killer (NK) cells, which express VLA-4, represent an innate barrier limiting spreading of melanoma under steady state conditions. Indeed, because of their expression of activating receptors, they are very efficient in recognizing and killing melanoma cells without the need of a previous priming...
December 2, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27884732/natural-killer-cell-subsets-and-receptor-expression-in-peripheral-blood-mononuclear-cells-of-a-healthy-korean-population-reference-range-influence-of-age-and-sex-and-correlation-between-nk-cell-receptors-and-cytotoxicity
#7
Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, Duck Cho
BACKGROUND: The purpose of this study was to identify CD56(bright) and CD56(dim) natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3(-)/CD56(dim) and CD3(-)/CD56(bright) NK cells in whole-blood samples from 122 healthy donors...
November 21, 2016: Human Immunology
https://www.readbyqxmd.com/read/27878235/accelerated-cell-cycle-progression-of-human-regulatory-t%C3%A2-cell-like-cell-line-caused-by-continuous-exposure-to-asbestos-fibers
#8
Suni Lee, Hidenori Matsuzaki, Megumi Maeda, Shoko Yamamoto, Naoko Kumagai-Takei, Tamayo Hatayama, Miho Ikeda, Kei Yoshitome, Yasumitsu Nishimura, Takemi Otsuki
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#9
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822754/roles-of-leptin-and-ghrelin-in-the-regulation-of-the-phenotype-and-cytokine-production-by-nk-cells-from-peripheral-blood
#10
S V Shirshev, I V Nekrasova, E G Orlova, O L Gorbunova
Both leptin and ghrelin used separately at the concentrations corresponding to trimesters II-III of pregnancy increase the number of CD56(bright) NK cells in mononuclear cell suspension; their combination also enhances the L-selectin expression on the surface of these cells in the culture. These hormones do not affect the production of TGF-β1, IL-17А, or IFN-γ by NK cells, and they inhibit the production of IL-10. Leptin decreses the IL-4 production by NKp46(+) cells, but the presence of ghrelin abrogates this effect...
September 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/27816327/nkp46-is-an-nk-cell-fungicidal-pattern-recognition-receptor
#11
Shu Shun Li, Christopher H Mody
Natural killer (NK) cells are an important contributor to innate host defense because of their role in direct microbial recognition and killing. Vitenshtein et al. make an important contribution by demonstrating that NK cells kill Candida glabrata using the NK activating receptor, NKp46, which recognizes the Epa adhesins.
November 2, 2016: Trends in Microbiology
https://www.readbyqxmd.com/read/27800305/notch-signaling-contributes-to-liver-inflammation-by-regulation-of-interleukin-22-producing-cells-in-hepatitis-b-virus-infection
#12
Xin Wei, Jiu-Ping Wang, Chun-Qiu Hao, Xiao-Fei Yang, Lin-Xu Wang, Chang-Xing Huang, Xue-Fan Bai, Jian-Qi Lian, Ye Zhang
The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4(+) T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27777574/phenotypic-and-functional-dysregulated-blood-nk-cells-in-colorectal-cancer-patients-can-be-activated-by-cetuximab-plus-il-2%C3%A2-or-il-15
#13
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27754869/the-stalk-domain-of-nkp30-contributes-to-ligand-binding-and-signaling-of-a-preassembled-nkp30-cd3%C3%AE-complex
#14
Stefanie Memmer, Sandra Weil, Steffen Beyer, Tobias Zöller, Eike Peters, Jessica Hartmann, Alexander Steinle, Joachim Koch
The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3ζ signaling remain unsolved. Here, we show that the stalk domain ((129)KEHPQLGAGTVLLLR(143)) of NKp30 is very sensitive to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3ζ for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27736647/nk-cell-recognition-of-candida-glabrata-through-binding-of-nkp46-and-ncr1-to-fungal-ligands-epa1-epa6-and-epa7
#15
Alon Vitenshtein, Yoav Charpak-Amikam, Rachel Yamin, Yoav Bauman, Batya Isaacson, Natan Stein, Orit Berhani, Liat Dassa, Moriya Gamliel, Chamutal Gur, Ariella Glasner, Carlos Gomez, Ronen Ben-Ami, Nir Osherov, Brendan P Cormack, Ofer Mandelboim
Natural killer (NK) cells form an important arm of the innate immune system and function to combat a wide range of invading pathogens, ranging from viruses to bacteria. However, the means by which NK cells accomplish recognition of pathogens with a limited repertoire of receptors remain largely unknown. In the current study, we describe the recognition of an emerging fungal pathogen, Candida glabrata, by the human NK cytotoxic receptor NKp46 and its mouse ortholog, NCR1. Using NCR1 knockout mice, we observed that this receptor-mediated recognition was crucial for controlling C...
October 12, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27717523/role-for-coronin-1-in-mouse-nk-cell-function
#16
Vincent Sam Yong Tchang, Michael Stiess, Kerstin Siegmund, Urs Karrer, Jean Pieters
Coronin 1, a member of the evolutionary conserved WD repeat protein family of coronin proteins is expressed in all leukocytes, but a role for coronin 1 in natural killer (NK) cell homeostasis and function remains unclear. Here, we have analyzed the number and functionality of NK cells in the presence and absence of coronin 1. In coronin 1-deficient mice, absolute NK cell numbers and phenotype were comparable to wild type mice in blood, spleen and liver. Following in vitro stimulation of the activating NK cell receptors NK1...
February 2017: Immunobiology
https://www.readbyqxmd.com/read/27683578/features-of-memory-like-and-pd-1-human-nk-cell-subsets
#17
REVIEW
Mariella Della Chiesa, Silvia Pesce, Letizia Muccio, Simona Carlomagno, Simona Sivori, Alessandro Moretta, Emanuela Marcenaro
Human NK cells are distinguished into CD56(bright)CD16(-) cells and CD56(dim)CD16(+) cells. These two subsets are conventionally associated with differential functional outcomes and are heterogeneous with respect to the expression of KIR and CD94/NKG2 heterodimers that represent the two major types of HLA-class I-specific receptors. Recent studies indicated that immature CD56(bright) NK cells, homogeneously expressing the inhibitory CD94/NKG2A receptor, are precursors of CD56(dim) NK cells that, in turn, during their process of differentiation, lose expression of CD94/NKG2A and subsequentially acquire inhibitory KIRs and LIR-1...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27662664/pd-1-mediates-functional-exhaustion-of-activated-nk-cells-in-patients-with-kaposi-sarcoma
#18
Asma Beldi-Ferchiou, Marion Lambert, Stéphanie Dogniaux, Frédéric Vély, Eric Vivier, Daniel Olive, Stéphanie Dupuy, Frank Levasseur, David Zucman, Céleste Lebbé, Damien Sène, Claire Hivroz, Sophie Caillat-Zucman
Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56dimCD16pos NK cells with otherwise normal expression of NK surface receptors...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27641642/altered-expression-of-natural-cytotoxicity-receptors-and-nkg2d-on-peripheral-blood-nk-cell-subsets-in-breast-cancer-patients
#19
Nayeli Goreti Nieto-Velázquez, Yessica Dorin Torres-Ramos, José Luis Muñoz-Sánchez, Lorena Espinosa-Godoy, Susana Gómez-Cortés, José Moreno, Mario Adán Moreno-Eutimio
Human natural killer (NK) cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy), 10 benign breast pathology patients, and 24 control individuals...
October 2016: Translational Oncology
https://www.readbyqxmd.com/read/27638120/bovine-natural-killer-cells-are-present-in-escherichia-coli-infected-mammary-gland-tissue-and-show-antimicrobial-activity-in-vitro
#20
Anja Sipka, Brianna Pomeroy, Suzanne Klaessig, Ynte Schukken
Natural killer (NK) cells are early responders in bacterial infections but their role in bovine mastitis has not been characterized. For the first time, we show the presence of NK cells (NKp46(+)/CD3(-)) in bovine mammary gland tissue after an intramammary challenge with Escherichia (E.) coli. A small number of NK cells was detected in milk from quarters before and during an E. coli challenge. In vitro cultures of primary bovine mammary gland epithelial cells stimulated with UV irradiated E. coli induced significant migration of peripheral blood NK cells (pbNK) within 2h...
October 2016: Comparative Immunology, Microbiology and Infectious Diseases
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