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Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis.
- Source :
-
Journal of Clinical Investigation . 7/17/2023, Vol. 133 Issue 14, p1-15. 16p. - Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*NEUTROPHILS
*SEPSIS
*BONE marrow
*RNA-binding proteins
*T cell receptors
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 133
- Issue :
- 14
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 165053561
- Full Text :
- https://doi.org/10.1172/JCI164585