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NK cell receptors

Katherine Walwyn-Brown, Karolin Guldevall, Mezida Saeed, Daniela Pende, Björn Önfelt, Andrew S MacDonald, Daniel M Davis
Cross-talk between NK cells and dendritic cells (DCs) is important in Th1 immune responses, including antitumor immunity and responses to infections. DCs also play a crucial role in polarizing Th2 immunity, but the impact of NK cell-DC interactions in this context remains unknown. In this study, we stimulated human monocyte-derived DCs in vitro with different pathogen-associated molecules: LPS or polyinosinic-polycytidylic acid, which polarize a Th1 response, or soluble egg Ag from the helminth worm Schistosoma mansoni , a potent Th2-inducing Ag...
August 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Seyed Ahmad Hoseinian, Davood Jafari, Mehdi Mahmoodi, Kamran Alimoghaddam, Mohammadreza Ostadali, Azita Talebzadeh Bonakdar, Arron Munggela Foma, Mir Saeed Yekaninejad, Ali Akbar Amirzargar
Background/aim: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies...
August 16, 2018: Turkish Journal of Medical Sciences
Angela Lombardi, Effie Tsomos, Sara S Hammerstad, Yaron Tomer
IFNα is a cytokine essential to a vast array of immunologic processes. Its induction early in the innate immune response provides a priming mechanism that orchestrates numerous subsequent pathways in innate and adaptive immunity. Despite its beneficial effects in viral infections IFNα has been reported to be associated with several autoimmune diseases including autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary cholangitis, and recently emerged as a major cytokine that triggers Type 1 Diabetes...
August 13, 2018: Journal of Autoimmunity
Koichi Sasaki, Yoshiki Miyashita, Daisuke Asai, Daiki Funamoto, Kazuki Sato, Yoko Yamaguchi, Yuji Mishima, Tadafumi Iino, Shigeo Takaishi, Jun Nagano, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama
Antibody-dependent cell-mediated cytotoxicity (ADCC) is caused by natural killer (NK) cells upon recognition of antigen-bound IgG via FcγRIIIa. This mechanism is crucial for cytolysis of pathogen-infected cells and monoclonal antibody (mAb)-mediated elimination of cancer cells. However, there is concern that mAb-based cancer therapy induces ADCC against non-target cells expressing antigens. To date, no strategy has been reported to enhance the selectivity of ADCC to protect non-target cells expressing antigens...
May 1, 2018: MedChemComm
Jinming Yang, Amrendra Kumar, Anna E Vilgelm, Sheau-Chiann Chen, Gregory D Ayers, Sergey V Novitskiy, Sebastian Joyce, Ann Richmond
The chemokine receptor, CXCR4, is involved in cancer growth, invasion, and metastasis. Several promising CXCR4 antagonists have been shown to halt tumor metastasis in preclinical studies, and clinical trials evaluating the effectiveness of these agents in cancer patients are ongoing. However, the impact of targeting CXCR4 specifically on immune cells is not clear. Here we demonstrate that genetic deletion of CXCR4 in myeloid cells (CXCR4MyeΔ/Δ) enhances the antitumor immune response, resulting in significantly reduced melanoma tumor growth...
August 14, 2018: Cancer Immunology Research
Yanjie Zhang, Chaoping Li, Mingzhi Zhang, Zhaoming Li
Extranodal NK/T cell lymphoma (NKTCL) is a rare but aggressive subtype of non-Hodgkin lymphoma. Multi-agent chemotherapy and involved-field radiotherapy are used to treat this disease, but the prognosis remains poor. Interleukin 13 and its receptors (IL-13Rs) are correlated with the pathogenesis and progression of various malignances. However, their roles in NKTCL have not been evaluated. In this study, we examined the roles of IL-13 and IL-13Rs in NKTCL and the underlying mechanisms. We found significantly higher serum IL-13 levels (p < 0...
August 11, 2018: Biochemical and Biophysical Research Communications
Bianca Simon, Manuel Wiesinger, Johannes März, Kilian Wistuba-Hamprecht, Benjamin Weide, Beatrice Schuler-Thurner, Gerold Schuler, Jan Dörrie, Ugur Uslu
Natural killer T (NKT) cells represent a cell subpopulation that combines characteristics of natural killer (NK) cells and T cells. Through their endogenous T-cell receptors (TCRs), they reveal a pronounced intrinsic anti-tumor activity. Thus, a NKT cell transfected with a chimeric antigen receptor (CAR), which recognizes a tumor-specific surface antigen, could attack tumor cells antigen-specifically via the CAR and additionally through its endogenous TCR. NKT cells were isolated from peripheral blood mononuclear cells (PBMCs), expanded, and electroporated with mRNA encoding a chondroitin sulfate proteoglycan 4 (CSPG4)-specific CAR...
August 11, 2018: International Journal of Molecular Sciences
Tomoko Miyata-Takata, Shih-Sung Chuang, Katsuyoshi Takata, Tomohiro Toji, Yoshinobu Maeda, Yasuharu Sato, Tadashi Yoshino
AIMS: Although the neoplastic cells of extranodal NK/T-cell lymphoma (ENKTL) usually do not express T-cell antigens, T-cell receptor (TCR) gene might be rearranged and TCR protein expressed. Downstream TCR pathway is important for the development of peripheral T-cell lymphoma (PTCL), but the expression of TCR pathway components has not been elucidated in ENKTL. METHODS AND RESULTS: We used formalin-fixed paraffin-embedded tissues from 91 ENKTL samples to immunohistochemically characterise the expression of TCR pathway components...
August 13, 2018: Histopathology
Laise Nayana Sala Elpidio, Josiane Bazzo de Alencar, Patrícia Yumeko Tsuneto, Hugo Vicentin Alves, Mariana Trento Toretta, Sérgio Ken It Taura, Jeane Eliete Laguila Visentainer, Ana Maria Sell
Polycystic ovary syndrome (PCOS) affects the endocrine system and is associated with low-grade inflammation. Natural killer (NK) cells are involved in the defense of the female reproductive tract, folliculogenesis, ovulation and the menstrual cycle. The killer-cell immunoglobulin-like receptors (KIR) on the surface of NK cells modulate the activation and function of these cells after interacting with human leukocyte antigen (HLA) class I ligands. The objective of this study was to evaluate the possible association of the KIR and their HLA ligands with polycystic ovary syndrome...
August 4, 2018: Journal of Reproductive Immunology
Qianyi He, Xiaojuan Shi, Bin Zhou, Junfang Teng, Chaoqi Zhang, Shasha Liu, Jingyao Lian, Benyan Luo, Guoqiang Zhao, Hong Lu, Yuming Xu, Yajun Lian, Yanjie Jia, Yi Zhang
Granulocytes and natural killer (NK) cells have been linked to brain injury in ischemic stroke. However, their recruitment from peripheral leucocytes in stroke patients is not well understood. Here, the expression of the interleukin 8 (CXCL8) in plasma, and CXC chemokine receptor 2 (CXCR2) in peripheral leucocytes of patients with ischemic stroke were evaluated. Based on the results, CXCR2 expression positively correlated with granulocytes and NK cells, which were in turn attracted by CXCL8. The results also indicated that CXCR2 was a direct target of microRNA (miR)-4437, a negative regulator of CXCR2, which was downregulated in peripheral leucocytes from patients with ischemic stroke...
August 7, 2018: Molecular Immunology
Josée Golay, Simona Martinelli, Rachele Alzani, Sabrina Cribioli, Clara Albanese, Elisa Gotti, Bruna Pasini, Benedetta Mazzanti, Riccardo Saccardi, Alessandro Rambaldi, Martino Introna
BACKGROUND: Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies. METHODS: CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)-derived CIKs...
August 6, 2018: Cytotherapy
Bronwyn M Gunn, Wen-Han Yu, Marcus M Karim, Jennifer M Brannan, Andrew S Herbert, Anna Z Wec, Peter J Halfmann, Marnie L Fusco, Sharon L Schendel, Karthik Gangavarapu, Tyler Krause, Xiangguo Qiu, Shinhua He, Jishnu Das, Todd J Suscovich, Jonathan Lai, Kartik Chandran, Larry Zeitlin, James E Crowe, Douglas Lauffenburger, Yoshihiro Kawaoka, Gary P Kobinger, Kristian G Andersen, John M Dye, Erica Ollmann Saphire, Galit Alter
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs...
August 8, 2018: Cell Host & Microbe
Lorenzo Mortara, Marzia B Gariboldi, Annalisa Bosi, Marco Bregni, Graziella Pinotti, Luigina Guasti, Alessandro Squizzato, Douglas M Noonan, Elena Monti, Leonardo Campiotti
BACKGROUND: Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is frequently added to chemotherapy in the treatment of colon cancer. OBJECTIVE: The present study evaluates the association between vitamin D serum levels and the ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer cell lines...
August 9, 2018: Targeted Oncology
Lucy C Walters, Karl Harlos, Simon Brackenridge, Daniel Rozbesky, Jordan R Barrett, Vitul Jain, Thomas S Walter, Chris A O'Callaghan, Persephone Borrow, Mireille Toebes, Scott G Hansen, Jonah Sacha, Shaheed Abdulhaqq, Justin M Greene, Klaus Früh, Emily Marshall, Louis J Picker, E Yvonne Jones, Andrew J McMichael, Geraldine M Gillespie
Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8+ T cells, respectively...
August 7, 2018: Nature Communications
Robert J Canter, William J Murphy
Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers...
August 7, 2018: Journal for Immunotherapy of Cancer
Rie Watanabe, Christina Eckstrand, Hongwei Liu, Niels C Pedersen
Laboratory cats were infected with a serotype I cat-passaged field strain of FIP virus (FIPV) and peritoneal cells harvested 2-3 weeks later at onset of lymphopenia, fever and serositis. Comparison peritoneal cells were collected from four healthy laboratory cats by peritoneal lavage and macrophages predominated in both populations. Differential mRNA expression analysis identified 5621 genes as deregulated in peritoneal cells from FIPV infected versus normal cats; 956 genes showed > 2.0 Log2 Fold Change (Log2 FC) and 1589 genes showed < -2...
August 7, 2018: Veterinary Research
Ye Li, David L Hermanson, Branden S Moriarity, Dan S Kaufman
Chimeric antigen receptors (CARs) significantly enhance the anti-tumor activity of immune effector cells. Although most studies have evaluated CAR expression in T cells, here we evaluate different CAR constructs that improve natural killer (NK) cell-mediated killing. We identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling. NK cells derived from human iPSCs that express this CAR (NK-CAR-iPSC-NK cells) have a typical NK cell phenotype and demonstrate improved anti-tumor activity compared with T-CAR-expressing iPSC-derived NK cells (T-CAR-iPSC-NK cells) and non-CAR-expressing cells...
August 2, 2018: Cell Stem Cell
M Z Luo, T Xu, X H Xue, Y P Wang, P L Wu, X M Chen, X M Tang, X D Zhao, Z Y Zhang
Objective: To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) . Methods: A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed...
August 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Masayuki Shiozawa, Chuan-Hsin Chang, Yi-Chun Huang, Yi-Ching Chen, Mau-Shin Chi, Hsu-Chao Hao, Yue-Cune Chang, Satoru Takeda, Kwan-Hwa Chi, Yu-Shan Wang
BACKGROUND: The natural killer cell line, NK-92MI, is cytotoxic against various types of cancer. The aim of this study was to develop chimeric antigen receptor-modified (CAR) NK-92MI cells targeting carcinoembryonic antigen-expressing (CEA) tumours and increase killing efficacy by pharmacologically modifying CEA-expression. RESULT: We generated anti-CEA-CAR NK-92MI cells by retroviral vector transduction. This genetically-modified cell line recognised and lysed high CEA-expressing tumour cell lines (LS174T) at 47...
August 3, 2018: BMC Immunology
Audrey Benyamine, Jérémy Magalon, Florence Sabatier, Luc Lyonnet, Stéphane Robert, Chloé Dumoulin, Sophie Morange, Karin Mazodier, Gilles Kaplanski, Martine Reynaud-Gaubert, Pascal Rossi, Françoise Dignat-George, Brigitte Granel, Pascale Paul
The pathophysiology of systemic sclerosis (SSc) involves early endothelial and immune activation, both preceding the onset of fibrosis. We previously identified soluble fractalkine and circulating endothelial microparticles (EMPs) as biomarkers of endothelial inflammatory activation in SSc. Fractalkine plays a dual role as a membrane-bound adhesion molecule expressed in inflamed endothelial cells (ECs) and as a chemokine involved in the recruitment, transmigration, and cytotoxic activation of immune cells that express CX3CR1, the receptor of fractalkine, namely CD8 and γδ T cells and natural killer (NK) cells...
2018: Frontiers in Immunology
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