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.

IF 1.6 4区 医学 Q3 OPHTHALMOLOGY
Cutaneous and Ocular Toxicology Pub Date : 2024-06-01 Epub Date: 2024-02-02 DOI:10.1080/15569527.2024.2310243
Laura Huth, Philipp M Amann, Yvonne Marquardt, Manuela Jansen, Jens Malte Baron, Sebastian Huth
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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.

在一种含有IL-23A反应性和IL-17A产生性γδ-T细胞的新型有机三维皮肤模型中了解利坦珠单抗对角质细胞衍生的IL-23A的影响。
目的为了研究抗IL-23A抗体利桑珠单抗对IL-36γ/IL-23A/IL-17A信号级联的影响,我们使用了一种新开发的由原代人类角质形成细胞、成纤维细胞和γδ-T细胞组成的三维皮肤模型。方法在这项体外研究中,我们开发了新的全厚三维皮肤模型,其中包含正常人表皮角质细胞(NHEK)、正常人真皮成纤维细胞(NHDF)以及对 IL-23A 有反应并能产生 IL-17A 的γδ-T 细胞。结果在初步的单层实验中,用 IL-23A 刺激γδ-T 细胞可促进 IL-17A 的表达,而利桑珠单抗治疗后可抑制 IL-17A 的表达。我们使用含有γδ-T细胞的三维皮肤模型发现,IL-36γ刺激不仅会显著增加IL-23A的表达,还会增加IL-17A的表达。结论我们的研究结果表明,阻断 IL-23A 对 IL-36γ/IL-23A 前馈环有抑制作用。我们新开发的三维皮肤模型含有对IL-23A有反应且能产生IL-17A的γδ-T细胞,可以对针对银屑病中IL-36γ/IL-23A/IL-17A信号级联的靶向疗法进行分子分析。
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来源期刊
CiteScore
3.30
自引率
6.20%
发文量
40
审稿时长
1 months
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.
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