{"doi":"10.21203/rs.2.21951/v2","title":"Transcriptomics of Type 2 Diabetic and Healthy Human Neutrophils","abstract":"<title>Abstract</title> <bold>Objectives: </bold>Chronic inflammatory diseases, including diabetes and cardiovascular disease, are heterogeneous and often co-morbid, with increasing global prevalence. Uncontrolled type 2 diabetes (T2D) can result in severe inflammatory complications. As neutrophils are essential to inflammation, we conducted RNA-seq transcriptomic analyses to investigate the association between neutrophil gene expression and T2D phenotype. Further, as specialized pro-resolving lipid mediators, including resolvin E1 (RvE1), can actively resolve inflammation, we further surveyed the impact of RvE1 on isolated neutrophils. <bold>Methods: </bold>Cell isolation and RNA-seq analysis of neutrophils from N=11 T2D and N=7 healthy individuals with available clinical data was conducted. Additionally, cultured neutrophils (N=3 T2D, N=3 healthy) were perturbed with increasing RvE1 doses (0nM, 1nM, 10nM, or 100nM) prior to RNA-seq. Data was evaluated through a bioinformatics pipeline including pathway analysis and post hoc false-discovery rate (FDR)-correction. <bold>Results: </bold>We observed significant differential expression of 50 genes between T2D and healthy neutrophils (p&lt;0.05), including decreased T2D gene expression in inflammatory- and lipid-related genes SLC9A4, NECTIN2 and PLPP3 (p&lt;0.003). RvE1 treatment induced dose-dependent differential gene expression (uncorrected p&lt;0.05) across groups, including 59 healthy and 216 T2D neutrophil genes. Comparing T2D to healthy neutrophils, 1097 genes were differentially expressed across RvE1 doses, including two significant genes, LILRB5 and AKR1C1 , involved in inflammation (p&lt;0.05). <bold>Conclusions: </bold>Inflammatory- and lipid-related genes were differentially expressed between T2D and healthy neutrophils, and RvE1 dose-dependently modified gene expression in both groups. Unraveling the mechanisms regulating abnormalities in diabetic neutrophil responses could lead to better diagnostics and therapeutics targeting inflammation and inflammation resolution.","journal":null,"year":2020,"id":133147,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":29130,"name":"Jamison McCorrison","orcid":"0000-0002-4807-0847","position":1,"is_corresponding":false},{"id":589487,"name":"Alaa Ahmed","orcid":null,"position":2,"is_corresponding":false},{"id":110428,"name":"Hatice Hastürk","orcid":"0000-0002-4395-3958","position":3,"is_corresponding":false},{"id":313416,"name":"Thomas E. Van Dyke","orcid":"0000-0003-0568-124X","position":4,"is_corresponding":false},{"id":347084,"name":"Marcelo Freire","orcid":"0000-0003-4906-7698","position":5,"is_corresponding":false},{"id":360853,"name":"Sarah E. Kleinstein","orcid":"0000-0002-9714-5155","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:16:17.577688Z","pmid":null,"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":[]}