title: Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis.
abstract: 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM 631, Campus de Luminy case 906, 13288 Marseille, France.
authors.forename: Baptiste N
authors.initials: BN
authors.lastname: Jaeger
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Céline
authors.initials: C
authors.lastname: Cognet
authors.forename: Claire
authors.initials: C
authors.lastname: Bernat
authors.forename: Diana
authors.initials: D
authors.lastname: Ordoñez-Rueda
authors.forename: Vincent
authors.initials: V
authors.lastname: Barlogis
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.forename: Emilie
authors.initials: E
authors.lastname: Narni-Mancinelli
authors.forename: Blandine
authors.initials: B
authors.lastname: Beaupain
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Marc
authors.initials: M
authors.lastname: Bajénoff
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Marie
authors.initials: M
authors.lastname: Malissen
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
mesh_terms: D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008875:Middle Aged; D009503:Neutropenia / Q000151:congenital / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D055815:Young Adult