Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2012

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

Vincent Barlogis
Marc Bajenoff
Bernard Malissen
Marie Malissen

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.

Domains

Immunology

Dates and versions

hal-00685480 , version 1 (05-04-2012)

Identifiers

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Baptiste N Jaeger, Jean Donadieu, Céline Cognet, Claire Bernat, Diana Ordoñez-Rueda, et al.. Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis.. Journal of Experimental Medicine, 2012, 209 (3), pp.565-80. ⟨10.1084/jem.20111908⟩. ⟨hal-00685480⟩
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