IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1.
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....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3756078?pdf=render |
| _version_ | 1819326970553434112 |
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| author | Stan de Kleijn Jeroen D Langereis Jenneke Leentjens Matthijs Kox Mihai G Netea Leo Koenderman Gerben Ferwerda Peter Pickkers Peter W M Hermans |
| author_facet | Stan de Kleijn Jeroen D Langereis Jenneke Leentjens Matthijs Kox Mihai G Netea Leo Koenderman Gerben Ferwerda Peter Pickkers Peter W M Hermans |
| author_sort | Stan de Kleijn |
| collection | DOAJ |
| description | 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-γ, but not IFN-α or IFN-β stimulated neutrophils, acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that IFN-γ-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. |
| first_indexed | 2024-12-24T13:03:24Z |
| format | Article |
| id | doaj.art-582d02cb1f4c4a78abe3a533e2d81527 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T13:03:24Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-582d02cb1f4c4a78abe3a533e2d815272022-12-21T16:54:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7224910.1371/journal.pone.0072249IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1.Stan de KleijnJeroen D LangereisJenneke LeentjensMatthijs KoxMihai G NeteaLeo KoendermanGerben FerwerdaPeter PickkersPeter W M HermansDuring 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-γ, but not IFN-α or IFN-β stimulated neutrophils, acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that IFN-γ-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.http://europepmc.org/articles/PMC3756078?pdf=render |
| spellingShingle | Stan de Kleijn Jeroen D Langereis Jenneke Leentjens Matthijs Kox Mihai G Netea Leo Koenderman Gerben Ferwerda Peter Pickkers Peter W M Hermans IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS ONE |
| title | IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. |
| title_full | IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. |
| title_fullStr | IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. |
| title_full_unstemmed | IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. |
| title_short | IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. |
| title_sort | ifn γ stimulated neutrophils suppress lymphocyte proliferation through expression of pd l1 |
| url | http://europepmc.org/articles/PMC3756078?pdf=render |
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