Understanding the impact of risankizumab on keratinocyte-derived IL-23A in a novel organotypic 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells.
Laura Huth, Philipp M Amann, Yvonne Marquardt, Manuela Jansen, Jens Malte Baron, Sebastian Huth
{"title":"Understanding the impact of risankizumab on keratinocyte-derived IL-23A in a novel organotypic 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells.","authors":"Laura Huth, Philipp M Amann, Yvonne Marquardt, Manuela Jansen, Jens Malte Baron, Sebastian Huth","doi":"10.1080/15569527.2024.2310243","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To study the effects of the anti-IL-23A antibody risankizumab on the IL-36γ/IL-23A/IL-17A signalling cascade we used a newly developed 3D skin model consisting of primary human keratinocytes, fibroblasts and γδ-T-cells.</p><p><strong>Methods: </strong>In this <i>in vitro</i> study we developed new full-thickness 3D skin models containing normal human epidermal keratinocytes (NHEK), normal human dermal fibroblasts (NHDF) and IL-23A responsive and IL-17A producing γδ-T-cells. The effects of IL-36γ stimulation with and without risankizumab treatment on IL-23A and IL-17A expression were examined at the RNA and protein levels.</p><p><strong>Results: </strong>In preliminary monolayer experiments stimulation of γδ-T-cells with IL-23A promoted the IL-17A expression that was inhibited after risankizumab treatment. Using 3D skin models containing γδ-T-cells, we found that stimulation with IL-36γ significantly increased not only IL-23A but also IL-17A expression. These effects were inhibited by concomitant treatment with risankizumab.</p><p><strong>Conclusions: </strong>Our results showed that blockade of IL-23A has inhibitory effects on the IL-36γ/IL-23A feedforward loop. Our newly developed 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells enables molecular analysis of targeted therapies aimed at the IL-36γ/IL-23A/IL-17A signalling cascade in psoriasis.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cutaneous and Ocular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15569527.2024.2310243","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: To study the effects of the anti-IL-23A antibody risankizumab on the IL-36γ/IL-23A/IL-17A signalling cascade we used a newly developed 3D skin model consisting of primary human keratinocytes, fibroblasts and γδ-T-cells.
Methods: In this in vitro study we developed new full-thickness 3D skin models containing normal human epidermal keratinocytes (NHEK), normal human dermal fibroblasts (NHDF) and IL-23A responsive and IL-17A producing γδ-T-cells. The effects of IL-36γ stimulation with and without risankizumab treatment on IL-23A and IL-17A expression were examined at the RNA and protein levels.
Results: In preliminary monolayer experiments stimulation of γδ-T-cells with IL-23A promoted the IL-17A expression that was inhibited after risankizumab treatment. Using 3D skin models containing γδ-T-cells, we found that stimulation with IL-36γ significantly increased not only IL-23A but also IL-17A expression. These effects were inhibited by concomitant treatment with risankizumab.
Conclusions: Our results showed that blockade of IL-23A has inhibitory effects on the IL-36γ/IL-23A feedforward loop. Our newly developed 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells enables molecular analysis of targeted therapies aimed at the IL-36γ/IL-23A/IL-17A signalling cascade in psoriasis.
期刊介绍:
Cutaneous and Ocular Toxicology is an international, peer-reviewed journal that covers all types of harm to cutaneous and ocular systems. Areas of particular interest include pharmaceutical and medical products; consumer, personal care, and household products; and issues in environmental and occupational exposures.
In addition to original research papers, reviews and short communications are invited, as well as concise, relevant, and critical reviews of topics of contemporary significance.