{"doi":"10.1172/jci164585","title":"Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis","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.","journal":"Journal of Clinical Investigation","year":2023,"id":320806,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247093,"name":"Monowar Aziz","orcid":"0000-0002-8195-4505","position":1,"is_corresponding":false},{"id":267009,"name":"Atsushi Murao","orcid":"0000-0001-9801-3923","position":2,"is_corresponding":false},{"id":1032090,"name":"Molly Kobritz","orcid":"0000-0002-4525-7112","position":3,"is_corresponding":false},{"id":336618,"name":"Andrew Shih","orcid":"0000-0001-8375-7313","position":4,"is_corresponding":false},{"id":497827,"name":"Robert P. Adelson","orcid":"0000-0002-0888-5638","position":5,"is_corresponding":false},{"id":280961,"name":"Max Brenner","orcid":"0000-0002-8010-148X","position":6,"is_corresponding":false},{"id":247094,"name":"Ping Wang","orcid":"0000-0002-1557-0394","position":7,"is_corresponding":false},{"id":318440,"name":"Hui Jin","orcid":"0000-0003-0297-3052","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:07:27.434133Z","pmid":"37463445","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}