IFN-c-Stimulated Neutrophils Suppress Lymphocyte Proliferation through Expression of PD-L1
نویسندگان
چکیده
During systemic inflammation different neutrophil subsets are mobilized to the peripheral blood. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16/CD62L), based on either an immature CD16/ CD62L or a CD16/CD62L phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex vivo, but how neutrophils become suppressive is unknown. We performed transcriptome analysis on the different neutrophil subsets to identify changes in mRNA expression that are relevant for their functions. Neutrophil subsets were isolated by fluorescence-activated cell sorting from blood of healthy volunteers that were administered a single dose of lipopolysaccharide (2 ng/kg i.v.) and the transcriptome was determined by microarray analysis. Interestingly, the CD16/CD62L suppressive neutrophils showed an interferon-induced transcriptome profile. More importantly, IFN-c, but not IFN-a or IFN-b stimulated neutrophils, acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that IFN-c-induced expression of PD-L1 on neutrophils enables suppression of lymphocyte proliferation. Specific stimulation of neutrophils present at the inflammatory sites might therefore have a pivotal role in regulating lymphocyte-mediated inflammation and autoimmune disease. Citation: de Kleijn S, Langereis JD, Leentjens J, Kox M, Netea MG, et al. (2013) IFN-c-Stimulated Neutrophils Suppress Lymphocyte Proliferation through Expression of PD-L1. PLoS ONE 8(8): e72249. doi:10.1371/journal.pone.0072249 Editor: Bernhard Ryffel, French National Centre for Scientific Research, France Received June 30, 2013; Accepted July 14, 2013; Published August 28, 2013 Copyright: 2013 de Kleijn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: SdK is supported by ZonMw, the Netherlands Grant No. 85100003. JL was supported by the Nano Cluster of Technology Foundation (STW FES0901: FES HTSM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] . These authors contributed equally to this work.
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During systemic inflammation different neutrophil subsets are mobilized to the peripheral blood. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16(bright)/CD62L(bright)), based on either an immature CD16(dim)/CD62L(bright) or a CD16(bright)/CD62L(dim) phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex viv...
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