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J Exp Med. 2012 Mar 12;209(3):565-80. doi: 10.1084/jem.20111908. Epub 2012 Mar 5.

Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis.

Author information

1
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM 631, Campus de Luminy case 906, 13288 Marseille, France.

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.

PMID:
22393124
PMCID:
PMC3302230
DOI:
10.1084/jem.20111908
[Indexed for MEDLINE]
Free PMC Article

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