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

Published in: Journal of Experimental Medicine, 2012, 209 (3), pp.565-80. ⟨10.1084/jem.20111908⟩

Authors: Baptiste N Jaeger, Jean Donadieu, Céline Cognet, Claire Bernat, Diana Ordoñez-Rueda, Vincent Barlogis, Nizar Mahlaoui, Aurore Fenis, Emilie Narni-Mancinelli, Blandine Beaupain, Christine Bellanné-Chantelot, Marc Bajenoff, Bernard Malissen, Marie Malissen, Eric Vivier, Sophie Ugolini

Summary

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.

Link to Pubmed [PMID] – 22393124

Link to HAL – hal-00685480

Link to DOI – 10.1084/jem.20111908