{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:07:50Z","timestamp":1789186070442,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014423","name":"Environmental Restoration and Conservation Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014423","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007467","name":"School of Medicine, Keio University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007467","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>IL\u201033 levels are elevated in the airways of patients with eosinophilic diseases, and IL\u201033 receptor expression on eosinophils is upregulated in type 2\u2010high environments. However, the role of IL\u201033 in the regulation of human eosinophils remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate the inflammatory effects of IL\u201033 on the cellular function of human eosinophils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood eosinophils were stimulated with IL\u201033, TNF\u2010\u03b1, oxidised low\u2010density lipoprotein (oxLDL) and complement fragments (C3a and C5a). Multi\u2010omics analyses, including transcriptomics and proteomics, were performed. Extracellular trap formation (ETosis) was assessed by SYTOX nucleic acid staining and was visualised by immunofluorescence and transmission electron microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multi\u2010omics analyses revealed an IL\u201033\u2010 and TNF\u2010\u03b1\u2010induced inflammatory gene signature characterised by the upregulation of cell surface markers (oxLDL receptor 1, CD22, CD4 and ICAM\u20101) and inflammatory mediators (C3, CCL3\/4 and IL1A\/B). CD22 upregulation was specific to IL\u201033 stimulation. Eosinophils derived from nasal polyps exhibited a gene expression profile similar to that of IL\u201033\u2010stimulated eosinophils. Functional assays demonstrated that oxLDL and complement fragments differentially prolonged eosinophil survival and altered the expression of adhesion molecules. OxLDL\u2010 and complement fragment\u2010induced gene signatures were partly detected in eosinophils derived from nasal polyps. Furthermore, IL\u201033 triggered ETosis via NADPH oxidase, mitogen\u2010activated protein kinase and phosphoinositide 3\u2010kinase pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL\u201033, in conjunction with oxLDL and the complement cascade, induces inflammatory changes in eosinophils, promoting an ETosis\u2010prone phenotype. These pathways represent potential therapeutic targets in refractory eosinophilic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70313","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:14:22Z","timestamp":1774412062000},"page":"3171-3184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>IL<\/scp>\n                    \u201033 Drives Inflammatory Changes and Extracellular Trap Formation in Eosinophils Involving Oxidised\n                    <scp>LDL<\/scp>\n                    and Complement Pathways"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-6184","authenticated-orcid":false,"given":"Emiko","family":"Matsuyama","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo 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