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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2023
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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. |
format | Online Article Text |
id | pubmed-10348768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
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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