Publication Date:
2012-01-24
Description:
Natural killer (NK) cells are lymphocytes involved in antimicrobial and antitumoral immune responses. Using N-ethyl-N-nitrosourea mutagenesis in mice, we identified a mutant with increased resistance to viral infections because of the presence of hyperresponsive NK cells. Whole-genome sequencing and functional analysis revealed a loss-of-function mutation in the Ncr1 gene encoding the activating receptor NKp46. The down-regulation of NK cell activity by NKp46 was associated with the silencing of the Helios transcription factor in NK cells. NKp46 was critical for the subsequent development of antiviral and antibacterial T cell responses, which suggests that the regulation of NK cell function by NKp46 allows for the optimal development of adaptive immune responses. NKp46 blockade enhanced NK cell reactivity in vivo, which could enable the design of immunostimulation strategies in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narni-Mancinelli, Emilie -- Jaeger, Baptiste N -- Bernat, Claire -- Fenis, Aurore -- Kung, Sam -- De Gassart, Aude -- Mahmood, Sajid -- Gut, Marta -- Heath, Simon C -- Estelle, Jordi -- Bertosio, Elodie -- Vely, Frederic -- Gastinel, Louis N -- Beutler, Bruce -- Malissen, Bernard -- Malissen, Marie -- Gut, Ivo G -- Vivier, Eric -- Ugolini, Sophie -- New York, N.Y. -- Science. 2012 Jan 20;335(6066):344-8. doi: 10.1126/science.1215621.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, Campus de Luminy case 906, 13288 Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267813" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptive Immunity
;
Amino Acid Substitution
;
Animals
;
Antibodies, Blocking/immunology
;
Antibodies, Monoclonal/immunology
;
Antigens, Ly/genetics/immunology/*physiology
;
CD8-Positive T-Lymphocytes/immunology
;
Cell Line
;
DNA-Binding Proteins/*genetics/physiology
;
Down-Regulation
;
Genetic Complementation Test
;
Herpesviridae Infections/*immunology/virology
;
Immunologic Memory
;
Killer Cells, Natural/*immunology
;
Listeriosis/immunology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Muromegalovirus/physiology
;
Mutagenesis
;
Natural Cytotoxicity Triggering Receptor 1/antagonists &
;
inhibitors/genetics/immunology/*physiology
;
T-Lymphocytes/*immunology
;
Transcription Factors/*genetics/physiology
;
Transcription, Genetic
;
Viral Load
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
