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Uncontrolled type 2 diabetes (T2D) can result in severe inflammatory complications. As neutrophils are essential to normal and aberrant inflammation, we conducted RNA-seq transcriptomic analyses to investigate the association between neutrophil gene expression and T2D phenotype. As specialized pro-resolving lipid mediators (SPM) act to resolve inflammation, we further surveyed the impact of neutrophil receptor binding SPM resolvin E1 (RvE1) on isolated diabetic and healthy neutrophils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cell isolation and RNA-seq analysis of neutrophils from\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200911 T2D and\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20097 healthy individuals with available clinical data was conducted. Additionally, cultured neutrophils (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20093 T2D, N\u2009=\u20093 healthy) were perturbed with increasing RvE1 doses (0\u2009nM, 1\u2009nM, 10\u2009nM, or 100\u2009nM) prior to RNA-seq. Data was evaluated through a bioinformatics pipeline including pathway analysis and post hoc false\u00a0discovery rate (FDR)-correction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed significant differential expression of 50 genes between T2D and healthy neutrophils (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), including decreased T2D gene expression in inflammatory- and lipid-related genes\n                      <jats:italic>SLC9A4, NECTIN2,<\/jats:italic>\n                      and\n                      <jats:italic>PLPP3<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.003). RvE1 treatment induced dose-dependent differential gene expression (uncorrected\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) 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,\n                      <jats:italic>LILRB5<\/jats:italic>\n                      and\n                      <jats:italic>AKR1C1<\/jats:italic>\n                      , involved in inflammation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The neutrophil transcriptomic database revealed novel chronic inflammatory- and lipid-related genes that were differentially expressed between T2D cells when compared to controls, and cells responded to RvE1 dose-dependently by gene expression changes. Unraveling the mechanisms regulating abnormalities in diabetic neutrophil responses could lead to better diagnostics and therapeutics targeting inflammation and inflammation resolution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12865-021-00428-6","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T05:03:03Z","timestamp":1623819783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptomics of type 2 diabetic and healthy human neutrophils"],"prefix":"10.1186","volume":"22","author":[{"given":"Sarah E.","family":"Kleinstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamison","family":"McCorrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Hasturk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-7698","authenticated-orcid":false,"given":"Marcelo","family":"Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"428_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","volume":"128","author":"K Ogurtsova","year":"2017","unstructured":"Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. 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