Fraillon Emma, Jégou Jean-François, Rabeony Hanitriniaina, Lecron Jean-Claude, Lebonvallet Nicolas, Marie-Joseph Emilie, Josset-Lamaugarny Audrey, Aimond Géraldine, Misery Laurent, Morel Franck, Chevalier Fabien P, Fromy Bérengère
Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, CNRS UMR5305, Université Claude Bernard Lyon 1, Lyon, France.
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, Université de Poitiers UR15560, Poitiers, France.
Sci Rep. 2025 Jul 23;15(1):26834. doi: 10.1038/s41598-025-12111-6.
Psoriasis is a chronic inflammatory skin disorder influenced by genetic and environmental factors. The imiquimod (IMQ)-induced mouse model is widely used to study psoriasis-like skin inflammation. However, its current use is largely limited to short treatment periods. Therefore, this model predominantly reflects acute inflammation and is limited in its capacity to capture the chronic nature of psoriasis. To date, little attention has been given to the extension of IMQ treatment duration to study the characteristics of sustained inflammation. This study aimed to provide the first direct comparison between short-term (ST, 4 days) and long-term (LT, 9 weeks) IMQ treatments on cutaneous histological, molecular and functional psoriasis features and to assess their similarity with human psoriasis. Both models demonstrated similar global severity, but with distinct features: ST-IMQ treatment led to increased epidermal hyperplasia and impaired skin barrier function, while LT-IMQ treatment was associated with greater desquamation and impaired suprabasal differentiation. Dermal mechanical properties and endothelial dysfunction were similar between the two models. Gene expression analysis revealed differentially expressed psoriasis-related markers between ST- and LT-IMQ treatments, with both models showing similarities to human psoriasis. These findings offer critical insights into how acute and chronic models can be tailored to study specific psoriasis features.
银屑病是一种受遗传和环境因素影响的慢性炎症性皮肤病。咪喹莫特(IMQ)诱导的小鼠模型被广泛用于研究银屑病样皮肤炎症。然而,目前其应用主要局限于短期治疗。因此,该模型主要反映急性炎症,在捕捉银屑病慢性特征方面能力有限。迄今为止,很少有人关注延长IMQ治疗时间以研究持续炎症的特征。本研究旨在首次直接比较短期(ST,4天)和长期(LT,9周)IMQ治疗对皮肤组织学、分子和功能性银屑病特征的影响,并评估它们与人类银屑病的相似性。两种模型均表现出相似的整体严重程度,但具有不同特征:ST-IMQ治疗导致表皮增生增加和皮肤屏障功能受损,而LT-IMQ治疗则与更大程度的脱屑和基底上层分化受损有关。两种模型之间的皮肤力学性能和内皮功能障碍相似。基因表达分析显示ST-和LT-IMQ治疗之间存在差异表达的银屑病相关标志物,两种模型均显示出与人类银屑病的相似性。这些发现为如何定制急性和慢性模型以研究特定的银屑病特征提供了关键见解。