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Article Dans Une Revue Journal of Leukocyte Biology Année : 2017

Neutrophils can disarm NK cell response through cleavage of NKp46

Résumé

Polymorphonuclear neutrophils (PMNs) can contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Mechanisms by which this immunoregulation process occurs remain incompletely understood. Here, we focused on the effect of human neutrophil-derived serine proteases on NKp46, a crucial activating receptor expressed on NK cells. We used flow cytometry, Western blotting, and mass spectrometry (MS) analysis to reveal that cathepsin G [CG; and not elastase or proteinase 3 (PR3)] induces a time- and concentration-dependent, down-regulatory effect on NKp46 expression through a restricted proteolytic mechanism. We also used a functional assay to demonstrate that NKp46 cleavage by CG severely impairs NKp46-mediated responses of NK cells, including IFN-γ production and cell degranulation. Importantly, sputa of cystic fibrosis (CF) patients, which have high concentrations of CG, also alter NKp46 on NK cells. Hence, we have identified a new immunoregulatory mechanism of neutrophils that proteolytically disarms NK cell responses.

Dates et versions

hal-03604688 , version 1 (10-03-2022)

Identifiants

Citer

Alexandre Valayer, Deborah Brea, Laurie Lajoie, Leslie Avezard, Lucie Combes-Soia, et al.. Neutrophils can disarm NK cell response through cleavage of NKp46. Journal of Leukocyte Biology, 2017, 101 (1), pp.253-259. ⟨10.1189/jlb.3AB0316-140RR⟩. ⟨hal-03604688⟩
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