{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:53:27Z","timestamp":1791132807854,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic rhinosinusitis with nasal polyp (CRSwNP) is a heterogeneous Type 2 inflammatory disease characterized by enhanced eosinophilic infiltration. Both innate and adaptive immunity are involved in the onset and progression of CRSwNP. Increased serum leptin levels are associated with various allergic conditions; however, the biological role of leptin in allergic immune cells requires further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effects of leptin on immune cells, including eosinophils, basophils, and mast cells, in CRSwNP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Leptin was used to stimulate eosinophils and eosinophilic cell lines, followed by analyses of gene expression, migration, and angiogenic capacity. Immunometabolic profile of CRSwNP, serum leptin, and galectin\u201010 levels were analyzed in conjunction with the gene expression profiles of nasal polyps. Furthermore, the biological effects of leptin on eosinophils were assessed using RNA sequencing and functional analyses, including a transwell migration assay and an angiogenesis assay via co\u2010culture with human umbilical vein endothelial cells (HUVEC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Increased serum leptin and galectin\u201010 levels were associated with Type 2 inflammatory markers and correlated with CRSwNP severity. RNA sequencing revealed upregulation of chemokine ligands in eosinophilic cell lines. Leptin induced plasminogen activator inhibitor 1 (PAI\u20101) expression in eosinophils but not in basophils or neutrophils. Leptin pretreatment substantially enhanced migration toward both C\u2013C motif chemokine ligand (CCL) 11 and CCL26 in eosinophilic cell lines. The leptin\u2010primed eosinophilic cell line promoted angiogenesis, as demonstrated in co\u2010culture with HUVECs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Leptin promotes eosinophil migration and angiogenesis, potentially via chemokine ligands and PAI\u20101 induction, and may promote CRSwNP progression under a Type 2 inflammatory milieu.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.70171","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:57:31Z","timestamp":1776427051000},"page":"1094-1106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leptin May Promote Eosinophilic CRSwNP Progression by Enhancing Eosinophil Chemotaxis and Angiogenesis Under a Type 2 Inflammatory Milieu"],"prefix":"10.1002","volume":"16","author":[{"given":"Yuki","family":"Sonoda","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"},{"name":"Immunology and Allergy Research Unit Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-0069","authenticated-orcid":false,"given":"Yohei","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"},{"name":"Immunology and Allergy Research Unit Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"},{"name":"Division of Molecular Genetics Research Center for Medical Science, The Jikei University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimasa","family":"Imoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Tamari","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Research Center for Medical Science, The Jikei University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Fujieda","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head &amp; Neck Surgery Faculty of Medical Sciences University of Fukui  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"issue":"29","key":"e_1_2_8_2_1","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens W. J.","year":"2020","journal-title":"Rhinology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.09.063"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21674"},{"issue":"4","key":"e_1_2_8_5_1","article-title":"Lung Function Impairment and Eosinophilia in Patients With Eosinophilic Chronic Rhinosinusitis","volume":"4","author":"Sonoda Y.","year":"2025","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13875"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.04.054"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.09.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.01.064"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.11.007"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-047230"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.70010"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-152-2-201001190-00008"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.12.001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.10.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.793607"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.10.039"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.118600"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12644"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0212074"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67289-8"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14120"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2015.7.5.421"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.01.027"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00538-7"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.02.016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.11.017"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1350"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01763-3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01925.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00482-x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.6.1911"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0499OC"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.09.041"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1994.tb00778.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00119"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.12.1092"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.046"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.02.018"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2012.09074.x"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.01.040"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0399OC"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22723"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.70171","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alr.70171","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.70171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:34:08Z","timestamp":1791131648000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.70171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/alr.70171"],"URL":"https:\/\/doi.org\/10.1002\/alr.70171","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}