{"title":"Leptin May Promote Eosinophilic CRSwNP Progression by Enhancing Eosinophil Chemotaxis and Angiogenesis Under a Type 2 Inflammatory Milieu.","authors":"Yuki Sonoda, Yohei Sato, Yoshimasa Imoto, Mayumi Tamari, Shigeharu Fujieda","doi":"10.1002/alr.70171","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To investigate the effects of leptin on immune cells, including eosinophils, basophils, and mast cells, in CRSwNP.</p><p><strong>Methods: </strong>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-10 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-culture with human umbilical vein endothelial cells (HUVEC).</p><p><strong>Results: </strong>Increased serum leptin and galectin-10 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-1) expression in eosinophils but not in basophils or neutrophils. Leptin pretreatment substantially enhanced migration toward both C-C motif chemokine ligand (CCL) 11 and CCL26 in eosinophilic cell lines. The leptin-primed eosinophilic cell line promoted angiogenesis, as demonstrated in co-culture with HUVECs.</p><p><strong>Conclusion: </strong>Leptin promotes eosinophil migration and angiogenesis, potentially via chemokine ligands and PAI-1 induction, and may promote CRSwNP progression under a Type 2 inflammatory milieu.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Forum of Allergy & Rhinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/alr.70171","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Objective: To investigate the effects of leptin on immune cells, including eosinophils, basophils, and mast cells, in CRSwNP.
Methods: 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-10 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-culture with human umbilical vein endothelial cells (HUVEC).
Results: Increased serum leptin and galectin-10 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-1) expression in eosinophils but not in basophils or neutrophils. Leptin pretreatment substantially enhanced migration toward both C-C motif chemokine ligand (CCL) 11 and CCL26 in eosinophilic cell lines. The leptin-primed eosinophilic cell line promoted angiogenesis, as demonstrated in co-culture with HUVECs.
Conclusion: Leptin promotes eosinophil migration and angiogenesis, potentially via chemokine ligands and PAI-1 induction, and may promote CRSwNP progression under a Type 2 inflammatory milieu.
期刊介绍：
International Forum of Allergy & Rhinologyis a peer-reviewed scientific journal, and the Official Journal of the American Rhinologic Society and the American Academy of Otolaryngic Allergy.
International Forum of Allergy Rhinology provides a forum for clinical researchers, basic scientists, clinicians, and others to publish original research and explore controversies in the medical and surgical treatment of patients with otolaryngic allergy, rhinologic, and skull base conditions. The application of current research to the management of otolaryngic allergy, rhinologic, and skull base diseases and the need for further investigation will be highlighted.
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