title: A selective role of NKG2D in inflammatory and autoimmune diseases.
abstract: The NKG2D activating receptor has been implicated in numerous autoimmune diseases. We tested the role of NKG2D in models of autoimmunity and inflammation using NKG2D knockout mice and antibody blockade experiments. The severity of experimental autoimmune encephalitis (EAE) was decreased in NKG2D-deficient mice when the disease was induced with a limiting antigen dose, but unchanged with an optimal antigen dose. Surprisingly, however, NKG2D deficiency had no detectable effect in several other models, including two models of type 1 diabetes, and a model of intestinal inflammation induced by poly(I:C). NKG2D antibody blockade in normal mice also failed to inhibit disease in the NOD diabetes model or the intestinal inflammation model. Published evidence using NKG2D knockout mice demonstrated a role for NKG2D in mouse models of atherosclerosis and liver inflammation, as well as in chronic obstructive pulmonary disease. Therefore, our results suggest that NKG2D plays selective roles in inflammatory diseases.
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.|Department of Life Science, Imperial College London, Imperial College Road, SW7 2AZ, London.
authors.forename: Nadia
authors.initials: N
authors.lastname: Guerra
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pestal
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Juarez
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beck
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Tkach
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cell Biology, and Cancer Research Laboratory, 489 Life Sciences, Addition, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Raulet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments; D011070:Poly I-C; D012720:Severity of Illness Index
chemical_list: D057134:Antibodies, Neutralizing; C527086:Klrk1 protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D011070:Poly I-C
keywords: EAE; Intestinal inflammation; NK cells; NKG2D; NOD; Natural Killer Group 2, member D; Natural Killer cells; RAE-1; Retinoic Acid Early Inducible Gene-1; Type 1 diabetes; poly(I:C); polyinosinic:polycytidylic acid.