IFN-gamma-Stimulated Neutrophils Suppress Lymphocyte Proliferation through Expression of PD-L1
SourcePLoS One, 8, 8, (2013), article e72249
Article / Letter to editor
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Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
SubjectDCN MP - Plasticity and memory N4i 1: Pathogenesis and modulation of inflammation; IGMD 7: Iron metabolism N4i 1: Pathogenesis and modulation of inflammation; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; DCN MP - Plasticity and memory N4i 1: Pathogenesis and modulation of inflammation; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism
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 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(bright)/CD62L(dim) suppressive neutrophils showed an interferon-induced transcriptome profile. More importantly, IFN-gamma, but not IFN-alpha or IFN-beta stimulated neutrophils, acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that IFN-gamma-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.
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