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    NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury


    Hoegl, Sandra and Ehrentraut, Heidi and Brodsky, Kelley S. and Victorino, Francisco and Golden‐Mason, Lucy and Eltzschig, Holger K. and McNamee, Eóin N. (2017) NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury. Journal of Leukocyte Biology, 101. pp. 471-480. ISSN 0741-5400

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    Abstract

    A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1‐inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin‐induced lung injury revealed a marked protection of Tbet−/− mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent studies identified natural killer (NK) cells as the major source of pulmonary Tbet during ALI. In addition, a chemokine screen suggested that mature Tbet+ NK‐cells are critical for the production of pulmonary CXCL1 and ‐2, thereby contributing to pulmonary PMN recruitment. Indeed, both NK‐cell Ab depletion and adoptive transfer studies provide evidence for NK cells in the orchestration of neutrophil recruitment during endotoxin‐induced ALI. Taken together, these findings identify a novel role for Tbet+ NK‐cells in initiating the early events of noninfectious pulmonary inflammation.

    Item Type: Article
    Keywords: mucosal; natural killer cell; chemokine; CXCR2; pulmonary inflammation;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11659
    Identification Number: https://doi.org/10.1189/jlb.3A0516-227R
    Depositing User: Eoin McNamee
    Date Deposited: 12 Nov 2019 12:05
    Journal or Publication Title: Journal of Leukocyte Biology
    Publisher: Society for Leukocyte Biology
    Refereed: Yes
    URI:

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