期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 209, 期 3, 页码 565-580出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20111908
关键词
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资金
- European Research Council
- MUGEN Network of Excellence and MASTERSWITCH from European Communities
- Fondation pour la Recherche Medicale
- ARC
- Agence Nationale de la Recherche
- Ligue Nationale contre le Cancer
- Axa Research Fund
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- Universite de la Mediterranee
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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