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

First Author  Jaeger BN Year  2012
Journal  J Exp Med Volume  209
Issue  3 Pages  565-80
PubMed ID  22393124 Mgi Jnum  J:182679
Mgi Id  MGI:5316324 Doi  10.1084/jem.20111908
Citation  Jaeger BN, et al. (2012) Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. J Exp Med 209(3):565-80
abstractText  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.
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