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NK cell receptors

Valéria de Lima Kaminski, Joel Henrique Ellwanger, Valeria Sandrim, Alessandra Pontillo, José Artur Bogo Chies
Pre-eclampsia (PE) is a hypertensive disorder that affects an important number of pregnant women worldwide. The exact causes of PE remain poorly understood. However, inflammation and deregulation of innate immune cells, such as natural killer (NK) cells, contribute to PE pathogenesis. Besides, the mother's genetic background also impacts on PE susceptibility. Thus, genetic variants that potentially modify the behaviour of inflammatory cells may help us to understand the causes of PE. Variants of genes encoding NKG2C (expressed in NK cells) and C-C chemokine receptor type 5 (CCR5) (expressed mainly in leucocytes) are important targets in the study of gestational disorders...
February 20, 2019: International Journal of Immunogenetics
Jianming Wu, Hemant K Mishra, Bruce Walcheck
Human NK cell antitumor activities involve Ab-dependent cell-mediated cytotoxicity (ADCC), which is a key mechanism of action for several clinically successful tumor-targeting therapeutic mAbs. Human NK cells exclusively recognize these Abs by the Fcγ receptor CD16A (FcγRIIIA), one of their most potent activating receptors. Unlike other activating receptors on NK cells, CD16A undergoes a rapid down-regulation in expression by a proteolytic process following NK cell activation with various stimuli. In this review, the role of a disintegrin and metalloproteinase-17 (ADAM17) in CD16A cleavage and as a regulatory checkpoint is discussed...
February 20, 2019: Journal of Leukocyte Biology
Matyas Meggyes, Eva Miko, Brigitta Szigeti, Nelli Farkas, Laszlo Szereday
BACKGROUND: Our goal with this study was to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerance mechanisms. METHODS: Thirteen healthy pregnant women and 10 non-pregnant controls were involved in this project. PBMCs and DICs were isolated from peripheral blood and from decidual tissues. After the characterization of different immune cell subsets, we used fluorochrome-conjugated monoclonal antibodies to measure the expression level of PD-1, PD-L1, NKG2D, and CD107a molecules by flow cytometry...
February 19, 2019: BMC Pregnancy and Childbirth
David J Flavell, Suzanne E Holmes, Sarah L Warnes, Sopsamorn U Flavell
We have previously shown that antibody-dependent cellular cytotoxicity (ADCC) cooperates with immunotoxin (IT)-mediated killing of human leukaemia cells in an severe combined immunodeficient (SCID) mouse model of human T-cell acute lymphoblastic leukaemia (SCID-HSB-2 mice), but not in an equivalent non-obese diabetic (NOD)/SCID mouse model. In these earlier studies, we reasoned that diminished ADCC due to the functional deficit in natural killer (NK) cell activity in NOD/SCID mice resulted in a failure of effective perforin/granzyme-mediated cytotoxicity necessary for the delivery of the augmentative effect...
February 16, 2019: Biomedicines
Sebastian Lunemann, Annika E Langeneckert, Gloria Martrus, Leonard U Hess, Wilhelm Salzberger, Annerose E Ziegler, Sebastian M Löbl, Tobias Poch, Gevitha Ravichandran, Jürgen Sauter, Alexander H Schmidt, Christoph Schramm, Karl J Oldhafer, Marcus Altfeld, Christian Körner
NK cells have been implicated to affect the outcome of numerous liver diseases. In particular, members of the killer-cell Ig-like receptor (KIR) family, predominantly expressed by NK cells, have been associated with the outcome of hepatitis C virus infection and clearance of hepatocellular carcinoma. Inhibitory KIRs tune NK cell function through interaction with HLA class I, a process termed education. Nevertheless, the impact of the hepatic environment on NK cell education is incompletely understood. Therefore, we investigated the composition and function of hepatic KIR-expressing NK cells...
February 19, 2019: Journal of Leukocyte Biology
Tong Chen, ChunYan Liu, LiJuan Li, Hui Liu, Ting Wang, ZongHong Shao, Rong Fu
INTRODUCTION: CD56bright NK cells have been highlighted to serve immunoregulatory functions. However, their roles in severe aplastic anemia (SAA) have not been elucidated. METHODS: Here, we investigated the quantities, phenotypes, cytokine secretion abilities, and the cytotoxicities of peripheral CD56bright NK cells along with CD56dim NK cells obtained from patients with SAA, SAA in remission (R-SAA), and healthy controls (HC). RESULTS: We observed the decreased quantities of CD56bright NK cells in SAA compared with in R-SAA and HC...
February 19, 2019: International Journal of Laboratory Hematology
Abdulbaset Mazarzaei, Mahtab Vafaei, Abdolmajid Ghasemian, Seyede Amene Mirforughi, Hassan Rajabi Vardanjani, Nada A S Alwan
Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV-infected cells. These cells identify and eliminate virus-infected cells in a multilateral manner, such as ligand stress, antibody-dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors...
February 18, 2019: Journal of Cellular Physiology
Yue Han, Fumou Sun, Xinrong Zhang, Tong Wang, Jiahao Jiang, Jialing Cai, Qi Gao, Kamal Hezam, Yali Liu, Jiajun Xie, Min Wang, Juan Zhang
PURPOSE: Bi-specific antibody (BsAb) is an emerging novel format of antibody. We aimed to develop the natural killer (NK) cell receptor NK group 2, member D (NKG2D)-mediated, immune surveillance system. In this system, the NKG2D ligand MHC class I-related chain A (MICA) was fused with BsAb, which targeted a cluster of differentiation 24 (CD24), a tumor-initiating cell marker that is over-expressed on hepatocellular carcinoma (HCC). METHODS: The Homo MICA extracellular domains (hMICA) were fused to the end of the heavy chain of cG7 with the flexible pentapeptide (Gly-Gly-Gly-Gly-Ser; G4S), which formed the cG7-MICA that was further identified using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting (WB)...
February 18, 2019: Journal of Cancer Research and Clinical Oncology
Simona Sivori, Paola Vacca, Genny Del Zotto, Enrico Munari, Maria Cristina Mingari, Lorenzo Moretta
NK cells play important roles in innate defenses against viruses and in the control of tumor growth and metastasis. The regulation/induction of NK cell function is mediated by an array of activating or inhibitory surface receptors. In humans, major activating receptors involved in target cell killing are the natural cytotoxicity receptors (NCRs) and NKG2D. Activating receptors recognize ligands that are overexpressed or expressed de novo upon cell stress, viral infection, or tumor transformation. The HLA-class I-specific inhibitory receptors, including KIRs recognizing HLA-class I allotypic determinants and CD94/NKG2A recognizing the class-Ib HLA-E, constitute a fail-safe mechanism to avoid unwanted NK-mediated damage to healthy cells...
February 18, 2019: Cellular & Molecular Immunology
Cynthia Perez, Kushal Prajapati, Brianna Burke, Lourdes Plaza-Rojas, Nancy J Zeleznik-Le, Jose A Guevara-Patino
BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling...
February 18, 2019: Journal for Immunotherapy of Cancer
Courtney B Crayne, Sabrin Albeituni, Kim E Nichols, Randy Q Cron
Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome (MAS) is a term used by rheumatologists to describe a potentially life-threatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus (SLE). Clinical and laboratory features of MAS include sustained fever, hyperferritinemia, pancytopenia, fibrinolytic coagulopathy, and liver dysfunction. Soluble interleukin-2 receptor alpha chain (sCD25) and sCD163 may be elevated, and histopathology often reveals characteristic increased hemophagocytic activity in the bone marrow (and other tissues), with positive CD163 (histiocyte) staining...
2019: Frontiers in Immunology
Rahul Pandey, Marina Bakay, Heather S Hain, Bryan Strenkowski, Anastasiya Yermakova, Jake A Kushner, Jordan S Orange, Hakon Hakonarson
CLEC16A locus polymorphisms have been associated with several autoimmune diseases. We overexpressed CLEC16A in YTS natural killer (NK) cells and observed reduced NK cell cytotoxicity and IFN-γ release, delayed dendritic cell (DC) maturation, decreased conjugate formation, cell-surface receptor downregulation and increased autophagy. In contrast, siRNA mediated knockdown resulted in increased NK cell cytotoxicity, reversal of receptor expression and disrupted mitophagy. Subcellular localization studies demonstrated that CLEC16A is a cytosolic protein that associates with Vps16A, a subunit of class C Vps-HOPS complex, and modulates receptor expression via autophagy...
2019: Frontiers in Immunology
Louise Lönndahl, Aram Rasul, Sol-Britt Lonne-Rahm, Mikael Holst, Björn Johansson, Husameldin El-Nour, Diana Radu Djurfeldt, Klas Nordlind
CONTEXT: Atopic dermatitis (AD) is a chronic, inflammatory, itching skin disorder, which may worsen due to stress, depression and anxiety. Tachykinins may be involved in inflammation signaling as well as they may have a role in stress, depression and anxiety. OBJECTIVE: This study aimed to measure the expression of tachykinin markers, in the skin of patients with AD, and the correlation of these tachykinins with clinical and psychodemographic parameters. MATERIALS AND METHODS: Twenty-eight adult patients with AD were investigated regarding tachykinin expression in skin biopsies, using an immunohistochemical technique...
February 18, 2019: Immunopharmacology and Immunotoxicology
Hong Cheng, Vered Schwell, Brett R Curtis, Ruzaliya Fazlieva, Heinrich Roder, Kerry S Campbell
KIR3DL1 is an inhibitory killer cell immunoglobulin-like receptor (KIR) that negatively regulates natural killer cell cytotoxicity. The KIR3DL1 cytoplasmic region (3DL1-cyto) is disordered and can be dissected into three segments: (I) H340-V351; (II) M352-D371; and (III) P372-P423. NMR studies indicate that segment II can dynamically adopt a loop-like conformation, and segments I and III can form dynamic helices that may mediate binding to membranes, particularly in the region around the N-terminal (N) immunoreceptor tyrosine-based inhibitory motif (ITIM), consistent with its role in signaling...
February 6, 2019: Structure
Giorgio Zenere, Omalla Allan Olwenyi, Siddappa N Byrareddy, Stephen E Braun
Natural killer (NK) cells are innate immune lymphocytes with a key role in host defense against HIV infection. Recent advances in chimeric antigen receptors (CARs) have made NK cells a prime target for expressing recombinant receptors capable of redirecting NK cytotoxic functions towards HIV-infected cells. In this review, we discuss the role of NK cells in HIV and the mechanisms of actions of HIV-targeting CAR strategies. Furthermore, we also review NK cells signal transduction and its application to CAR NK cell strategies to develop new combinations of CAR intracellular domains and to improve CAR NK signaling and cytotoxic functions...
February 13, 2019: Drug Discovery Today
Antje Mohs, Nadine Kuttkat, Tobias Otto, Sameh A Youssef, Alain De Bruin, Christian Trautwein
In Western countries, a rising incidence of obesity and type 2 diabetes correlates with an increase of non-alcoholic steatohepatitis (NASH)-a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). NASH is associated with chronic liver injury, triggering hepatocyte death and enhanced translocation of intestinal bacteria, leading to persistent liver inflammation through activation of Toll-like receptors and their adapter protein myeloid differentiation factor 88 (MyD88). Therefore, we investigated the role of MyD88 during progression from NASH to HCC using a mouse model of chronic liver injury (hepatocyte-specific deletion of nuclear factor κB essential modulator, Nemo; NemoΔhepa)...
February 13, 2019: Carcinogenesis
Ching-Yen Lin, Celeste Alexander, Andrew J Steelman, Chiristine M Warzecha, Maria R C de Godoy, Kelly S Swanson
Yeast products may serve as functional ingredients due to their benefits on host health, but vary greatly in source, composition, and functionality, justifying research in host species of interest. In this study, a Saccharomyces cerevisiae fermentation product (SCFP) was investigated as a dietary supplement for adult dogs. Adult female beagles (n = 12; mean age = 3.3 ± 0.8 yr; mean BW = 10.3 ± 0.68 kg) were fed the same diet, but supplemented with 3 levels of SCFP (125, 250 and 500 mg/d) or a placebo (sucrose) via gelatin capsules in a replicated 4 x 4 Latin square design...
February 16, 2019: Journal of Animal Science
Yasuhiro Shimojima, Dai Kishida, Ken-Ichi Ueno, Satoru Ushiyama, Takanori Ichikawa, Yoshiki Sekijima
OBJECTIVE: To investigate the characteristics of circulating NK cells and their IFN-γ-producing ability in adult-onset Still's disease (AOSD). METHODS: Peripheral blood mononuclear cells were obtained from 22 patients in the acute phase of AOSD (acute AOSD); 7 of the 22 patients after treatment (remission AOSD), and 11 healthy controls (HC). NK cells and their IFN-γ expression levels were analyzed by flow cytometry. Additionally, the cytokine receptors of interleukin (IL)-12, IL-15, and IL-18 on NK cells were also evaluated...
February 15, 2019: Journal of Rheumatology
Qinglai Meng, Asifa K Zaidi, John Sedy, Armand Bensussan, Daniel L Popkin
CD160 is highly expressed by NK cells and is associated with cytolytic effector activity. Herpes virus entry mediator (HVEM) activates NK cells for cytokine production and cytolytic function via CD160. Fc-fusions are a well-established class of therapeutics, where the Fc domain provides additional biological and pharmacological properties to the fusion protein including enhanced serum t 1/2 and interaction with Fc receptor-expressing immune cells. We evaluated the specific function of HVEM in regulating CD160-mediated NK cell effector function by generating a fusion of the HVEM extracellular domain with human IgG1 Fc bearing CD16-binding mutations (Fc*) resulting in HVEM-(Fc*)...
February 15, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Hampartsoum B Barsoumian, Lalit Batra, Pradeep Shrestha, William S Bowen, Hong Zhao, Nejat K Egilmez, Jorge G Gomez-Gutierrez, Esma S Yolcu, Haval Shirwan
: Costimulation through 4-1BB (CD137) receptor generates robust CD8+ T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Here, we report that treatment with an oligomeric form of the ligand, SA-4-1BBL, as a single agent is able to protect mice against subsequent tumor challenge irrespective of the tumor type...
February 15, 2019: Cancer Research
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