title: Targeting natural killer cell reactivity by employing antibody to NKp46: implications for type 1 diabetes.
abstract: Natural killer (NK) cells belong to the innate lymphoid cells. Their cytotoxic activity is regulated by the delicate balance between activating and inhibitory signals. NKp46 is a member of the primary activating receptors of NK cells. We previously reported that the NKp46 receptor is involved in the development of type 1 diabetes (T1D). Subsequently, we hypothesized that blocking this receptor could prevent or hinder disease development. To address this goal, we developed monoclonal antibodies for murine NKp46. One mAb, named NCR1.15, recognizes the mouse homologue protein of NKp46, named Ncr1, and was able to down-regulate the surface expression of NKp46 on primary murine NK cells following antibody injection in vivo. Additionally, NCR1.15 treatments were able to down-regulate cytotoxic activity mediated by NKp46, but not by other NK receptors. To test our primary assumption, we examined T1D development in two models, non-obese diabetic mice and low-dose streptozotocin. Our results show a significantly lower incidence of diabetic mice in the NCR1.15-treated group compared to control groups. This study directly demonstrates the involvement of NKp46 in T1D development and suggests a novel treatment strategy for early insulitis.
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Rami
authors.initials: R
authors.lastname: Yossef
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel; Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Avishai
authors.initials: A
authors.lastname: Shemesh
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Guttman
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Uzi
authors.initials: U
authors.lastname: Hadad
authors.affiliation: BioLineRx Ltd., 19 Hartum Street, P.O. Box 45158. Jerusalem 91450, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Nedvetzki
authors.affiliation: Center for Proteomics and Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Antonija
authors.initials: A
authors.lastname: Miletić
authors.affiliation: Pathology Department, Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Karen
authors.initials: K
authors.lastname: Nalbandyan
authors.affiliation: Innate Immunity Group, German Cancer Research Center, Heidelberg 69120, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Cerwenka
authors.affiliation: Center for Proteomics and Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport
chemical_list: D019138:Antibodies, Blocking; D055627:Natural Cytotoxicity Triggering Receptor 1