title: The activating receptor NKp46 is essential for the development of type 1 diabetes.
abstract: The mechanism of action of natural killer (NK) cells in type 1 diabetes is still unknown. Here we show that the activating receptor NKp46 recognizes mouse and human ligands on pancreatic beta cells. NK cells appeared in the pancreas when insulitis progressed to type 1 diabetes, and NKp46 engagement by beta cells led to degranulation of NK cells. NKp46-deficient mice had less development of type 1 diabetes induced by injection of a low dose of streptozotocin. Injection of soluble NKp46 proteins into nonobese diabetic mice during the early phase of insulitis and the prediabetic stage prevented the development of type 1 diabetes. Our findings demonstrate that NKp46 is essential for the development of type 1 diabetes and highlight potential new therapeutic modalities for this disease.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Institute for Medical Research Israel-Canada, Jerusalem, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Moran
authors.initials: M
authors.lastname: Elboim
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Saar
authors.initials: S
authors.lastname: Mizrahi
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.forename: Hormas
authors.initials: H
authors.lastname: Ghadially
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Tomer
authors.initials: T
authors.lastname: Nir
authors.forename: Victoria
authors.initials: V
authors.lastname: Doviner
authors.forename: Oren
authors.initials: O
authors.lastname: Hershkovitz
authors.forename: Michal
authors.initials: M
authors.lastname: Mendelson
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Naparstek
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D001324:Autoantigens; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse