{"doi":"10.1101/2024.09.06.611551","title":"The Cardioprotective Role of Neutrophil-Specific STING in Myocardial Ischemia/Reperfusion Injury","abstract":"Background: Neutrophils are the most rapid and abundant immune cells to infiltrate the myocardium following myocardial ischemia/reperfusion injury (MI/R). Neutrophil heterogeneity has not been well characterized in MI/R, and studies have shown conflicting results regarding the impact of neutrophil depletion on cardiac injury. We thus aim to study the impact of neutrophils with enriched type I interferon signature and the role of STING (stimulator of interferon genes) signaling in neutrophils on cardiac reperfusion injury. Methods: We utilized single-cell RNA sequencing to study neutrophil heterogeneity in response to MI/R. We generated a neutrophil-specific STING knockout mouse to assess the role of neutrophil STING in a model of MI/R. We examined cardiac function following injury via echocardiography and assessed the immune cell trajectory following injury utilizing flow cytometry. Results: We identified a population of neutrophils with enriched type I interferon signaling and response to type I interferon following MI/R. We found that genetic deletion of neutrophil-specific STING led to worsened cardiac function following MI/R. Further investigation of the immune response by flow cytometry revealed decreased neutrophil infiltration into the myocardium and a shift in macrophage polarization. Conclusions: Our findings suggest that neutrophil-specific STING is cardioprotective in MI/R, partly due to its effects on downstream immune cells. These results demonstrate that early alterations or therapeutic interventions can influence key events in the resolution of inflammation following MI/R.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491825,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1337728,"name":"Triniti Scruggs","orcid":null,"position":1,"is_corresponding":false},{"id":244978,"name":"Lanfang Wang","orcid":"0000-0003-1228-4613","position":2,"is_corresponding":false},{"id":686661,"name":"Gabriella Kabboul","orcid":"0000-0002-4784-2307","position":3,"is_corresponding":false},{"id":407559,"name":"John W. Calvert","orcid":"0000-0001-6858-6042","position":4,"is_corresponding":false},{"id":244984,"name":"Rebecca D. Levit","orcid":"0000-0001-5405-8716","position":5,"is_corresponding":false},{"id":1202838,"name":"Maegan L. Brockman","orcid":"0000-0002-2716-2953","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:08:45.247225Z","pmid":"39314411","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":[]}