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Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis
Natural killer (NK) cells are bone marrow (BM)–derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302230/ https://www.ncbi.nlm.nih.gov/pubmed/22393124 http://dx.doi.org/10.1084/jem.20111908 |
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author | Jaeger, Baptiste N. Donadieu, Jean Cognet, Céline Bernat, Claire Ordoñez-Rueda, Diana Barlogis, Vincent Mahlaoui, Nizar Fenis, Aurore Narni-Mancinelli, Emilie Beaupain, Blandine Bellanné-Chantelot, Christine Bajénoff, Marc Malissen, Bernard Malissen, Marie Vivier, Eric Ugolini, Sophie |
author_facet | Jaeger, Baptiste N. Donadieu, Jean Cognet, Céline Bernat, Claire Ordoñez-Rueda, Diana Barlogis, Vincent Mahlaoui, Nizar Fenis, Aurore Narni-Mancinelli, Emilie Beaupain, Blandine Bellanné-Chantelot, Christine Bajénoff, Marc Malissen, Bernard Malissen, Marie Vivier, Eric Ugolini, Sophie |
author_sort | Jaeger, Baptiste N. |
collection | PubMed |
description | Natural killer (NK) cells are bone marrow (BM)–derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation and poor survival and were blocked at an immature stage associated with hyporesponsiveness. The role of neutrophils as key regulators of NK cell functions was confirmed in patients with severe congenital neutropenia and autoimmune neutropenia. In addition to their direct antimicrobial activity, mature neutrophils are thus endowed with immunoregulatory functions that are conserved across species. These findings reveal novel types of cooperation between cells of the innate immune system and prompt examination of NK cell functional deficiency in patients suffering from neutropenia-associated diseases. |
format | Online Article Text |
id | pubmed-3302230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33022302012-09-12 Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis Jaeger, Baptiste N. Donadieu, Jean Cognet, Céline Bernat, Claire Ordoñez-Rueda, Diana Barlogis, Vincent Mahlaoui, Nizar Fenis, Aurore Narni-Mancinelli, Emilie Beaupain, Blandine Bellanné-Chantelot, Christine Bajénoff, Marc Malissen, Bernard Malissen, Marie Vivier, Eric Ugolini, Sophie J Exp Med Article Natural killer (NK) cells are bone marrow (BM)–derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation and poor survival and were blocked at an immature stage associated with hyporesponsiveness. The role of neutrophils as key regulators of NK cell functions was confirmed in patients with severe congenital neutropenia and autoimmune neutropenia. In addition to their direct antimicrobial activity, mature neutrophils are thus endowed with immunoregulatory functions that are conserved across species. These findings reveal novel types of cooperation between cells of the innate immune system and prompt examination of NK cell functional deficiency in patients suffering from neutropenia-associated diseases. The Rockefeller University Press 2012-03-12 /pmc/articles/PMC3302230/ /pubmed/22393124 http://dx.doi.org/10.1084/jem.20111908 Text en © 2012 Jaeger et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Jaeger, Baptiste N. Donadieu, Jean Cognet, Céline Bernat, Claire Ordoñez-Rueda, Diana Barlogis, Vincent Mahlaoui, Nizar Fenis, Aurore Narni-Mancinelli, Emilie Beaupain, Blandine Bellanné-Chantelot, Christine Bajénoff, Marc Malissen, Bernard Malissen, Marie Vivier, Eric Ugolini, Sophie Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title | Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title_full | Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title_fullStr | Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title_full_unstemmed | Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title_short | Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
title_sort | neutrophil depletion impairs natural killer cell maturation, function, and homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302230/ https://www.ncbi.nlm.nih.gov/pubmed/22393124 http://dx.doi.org/10.1084/jem.20111908 |
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