ArticleThe Journal of clinical investigation2023
Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- CD4Sensors (Basel, Switzerland) · 2026Pooled it
- Role of DLL4 in Neutrophil Aging and Impaired Clearance in Sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Single-cell transcriptomic analysis reveals immune remodeling in bone marrow during aged sepsis.GeroScience · 2026Article
- Age but not sex modifies lymphoid immune responses in murine sepsis.Research square · 2026Article
- Review
- Article
- Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in pneumonia-associated sepsis.Nature communications · 2026Article
- Identification and Validation of Liver Transplantation-Induced Acute Lung Injury Biomarkers Using a Bioinformatics and Experimental Approach.Annals of transplantation · 2026Article
- Mitochondrial dysfunction in sepsis-induced immunoparalysis: from immune-cell metabolic reprogramming to clinical biomarkers.Frontiers in immunology · 2026Review
- T cell exhaustion in sepsis: mechanisms, biomarkers, and immune-reversal strategies.Frontiers in immunology · 2026Review
- Neutrophil in sepsis: functional aberration and regulated cell death.Frontiers in immunology · 2026Review
- DLL4+ neutrophils promote Notch1-mediated endothelial PANoptosis to exacerbate acute lung injury in sepsis.The Journal of clinical investigation · 2025Article
- Major histocompatibility complex class II-expressing bone marrow megakaryocytes activate CD4bioRxiv : the preprint server for biology · 2025Article
- Gut-primed neutrophils activate Kupffer cells to promote hepatic injury in mouse sepsis.Nature communications · 2025Article
- SAA1/FPR2 signaling between keratinocytes and neutrophils sustains chronic inflammation in Sweet syndrome.The Journal of clinical investigation · 2025Article
- Neutrophils in the Bone Marrow Express DEC205, Guiding Their Migration to Inflamed Tissues.Immunology · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- Extracellular Cold-Inducible RNA-Binding Protein: Progress from Discovery to Present.International journal of molecular sciences · 2025Review
- Metabolic phenotype of bovine blood-derived neutrophils is altered in milk.Scientific reports · 2025Article
- Combination therapy with lipid prodrug liposomes reshapes disease-associated neutrophils to promote the cancer-immunity cycle.Journal of nanobiotechnology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.