| First Author | Jin H | Year | 2023 |
| Journal | J Clin Invest | Volume | 133 |
| Issue | 14 | PubMed ID | 37463445 |
| Mgi Jnum | J:338362 | Mgi Id | MGI:7511372 |
| Doi | 10.1172/JCI164585 | Citation | Jin H, et al. (2023) Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis. J Clin Invest 133(14) |
| abstractText | 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-gamma via IL-12. BMDNs stimulated with eCIRP and IFN-gamma underwent hyper-NETosis. Stimulating human peripheral blood neutrophils with eCIRP also induced APANs, and stimulating human neutrophils with eCIRP and IFN-gamma 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-gamma-mediated hyper-NETosis. |
