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Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis

Extracellular cold-inducible RNA-binding protein (eCIRP) is a key mediator of severity and mortality in sepsis. We found that stimulation of mouse bone marrow–derived neutrophils (BMDNs) with eCIRP generated a distinct neutrophil subpopulation, characterized by cell surface markers of both antigen-p...

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Autores principales: Jin, Hui, Aziz, Monowar, Murao, Atsushi, Kobritz, Molly, Shih, Andrew J., Adelson, Robert P., Brenner, Max, Wang, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348768/
https://www.ncbi.nlm.nih.gov/pubmed/37463445
http://dx.doi.org/10.1172/JCI164585
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author Jin, Hui
Aziz, Monowar
Murao, Atsushi
Kobritz, Molly
Shih, Andrew J.
Adelson, Robert P.
Brenner, Max
Wang, Ping
author_facet Jin, Hui
Aziz, Monowar
Murao, Atsushi
Kobritz, Molly
Shih, Andrew J.
Adelson, Robert P.
Brenner, Max
Wang, Ping
author_sort Jin, Hui
collection PubMed
description Extracellular cold-inducible RNA-binding protein (eCIRP) is a key mediator of severity and mortality in sepsis. We found that stimulation of mouse bone marrow–derived neutrophils (BMDNs) with eCIRP generated a distinct neutrophil subpopulation, characterized by cell surface markers of both antigen-presenting cells and aged neutrophils as well as expression of IL-12, which we named antigen-presenting aged neutrophils (APANs). The frequency of APANs was significantly increased in the blood, spleen, and lungs of WT mice subjected to cecal ligation and puncture–induced sepsis but not in CIRP(–/–) mice. Patients with sepsis had a significant increase in circulating APAN counts compared with healthy individuals. Compared with non–APAN-transfered mice, APAN-transferred septic mice had increased serum levels of injury and inflammatory markers, exacerbated acute lung injury (ALI), and worsened survival. APANs and CD4(+) T cells colocalized in the spleen, suggesting an immune interaction between these cells. APANs cocultured with CD4(+) T cells significantly induced the release of IFN-γ via IL-12. BMDNs stimulated with eCIRP and IFN-γ underwent hyper-NETosis. Stimulating human peripheral blood neutrophils with eCIRP also induced APANs, and stimulating human neutrophils with eCIRP and IFN-γ caused hyper-NETosis. Thus, eCIRP released during sepsis induced APANs to aggravate ALI and worsen the survival of septic animals via CD4(+) T cell activation, Th1 polarization, and IFN-γ–mediated hyper-NETosis.
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spelling pubmed-103487682023-07-17 Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis Jin, Hui Aziz, Monowar Murao, Atsushi Kobritz, Molly Shih, Andrew J. Adelson, Robert P. Brenner, Max Wang, Ping J Clin Invest Research Article Extracellular cold-inducible RNA-binding protein (eCIRP) is a key mediator of severity and mortality in sepsis. We found that stimulation of mouse bone marrow–derived neutrophils (BMDNs) with eCIRP generated a distinct neutrophil subpopulation, characterized by cell surface markers of both antigen-presenting cells and aged neutrophils as well as expression of IL-12, which we named antigen-presenting aged neutrophils (APANs). The frequency of APANs was significantly increased in the blood, spleen, and lungs of WT mice subjected to cecal ligation and puncture–induced sepsis but not in CIRP(–/–) mice. Patients with sepsis had a significant increase in circulating APAN counts compared with healthy individuals. Compared with non–APAN-transfered mice, APAN-transferred septic mice had increased serum levels of injury and inflammatory markers, exacerbated acute lung injury (ALI), and worsened survival. APANs and CD4(+) T cells colocalized in the spleen, suggesting an immune interaction between these cells. APANs cocultured with CD4(+) T cells significantly induced the release of IFN-γ via IL-12. BMDNs stimulated with eCIRP and IFN-γ underwent hyper-NETosis. Stimulating human peripheral blood neutrophils with eCIRP also induced APANs, and stimulating human neutrophils with eCIRP and IFN-γ caused hyper-NETosis. Thus, eCIRP released during sepsis induced APANs to aggravate ALI and worsen the survival of septic animals via CD4(+) T cell activation, Th1 polarization, and IFN-γ–mediated hyper-NETosis. American Society for Clinical Investigation 2023-07-17 /pmc/articles/PMC10348768/ /pubmed/37463445 http://dx.doi.org/10.1172/JCI164585 Text en © 2023 Jin et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Jin, Hui
Aziz, Monowar
Murao, Atsushi
Kobritz, Molly
Shih, Andrew J.
Adelson, Robert P.
Brenner, Max
Wang, Ping
Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title_full Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title_fullStr Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title_full_unstemmed Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title_short Antigen-presenting aged neutrophils induce CD4(+) T cells to exacerbate inflammation in sepsis
title_sort antigen-presenting aged neutrophils induce cd4(+) t cells to exacerbate inflammation in sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348768/
https://www.ncbi.nlm.nih.gov/pubmed/37463445
http://dx.doi.org/10.1172/JCI164585
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