{"title":"IL-34 is expressed in the pancreas and regulates local inflammation","authors":"Chloé M Delépine , Emilie Courty , Laurence Preisser , Raffaella Soleti , Laetitia Basset , Audrey Le Guernic , Laure Rolland , Marine Monnier , Gianni Pasquetti , Simon Blanchard , Pascale Pignon , Nathalie Merillon , Julie Kerr-Conte , Charline Miot , Dominique Couez , Aline Schmidt-Tanguy , Elise Dalmas , Pascale Jeannin , Jean-Sébastien Annicotte , Yves Delneste , Celine Beauvillain","doi":"10.1016/j.trsl.2025.07.002","DOIUrl":null,"url":null,"abstract":"<div><div>Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of <em>Il34</em> in mice (IL-34<sup>ΔPdx</sup>) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34<sup>ΔPdx</sup> mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, <em>ex vivo</em> murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of <em>Il-34</em> mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 56-67"},"PeriodicalIF":5.9000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1931524425000763","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of Il34 in mice (IL-34ΔPdx) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34ΔPdx mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, ex vivo murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of Il-34 mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.
期刊介绍:
Translational Research (formerly The Journal of Laboratory and Clinical Medicine) delivers original investigations in the broad fields of laboratory, clinical, and public health research. Published monthly since 1915, it keeps readers up-to-date on significant biomedical research from all subspecialties of medicine.