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慢性皮肤炎症性疾病的特征差异在皮肤人源化银屑病和特应性皮炎小鼠模型中显现。

Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.

机构信息

Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain.

Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain; Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain.

出版信息

J Invest Dermatol. 2016 Jan;136(1):136-45. doi: 10.1038/JID.2015.362.

Abstract

Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing.

摘要

银屑病和特应性皮炎是影响全球大量患者的慢性复发性皮肤炎症性疾病。银屑病的特征是辅助性 T 细胞 1 型和/或辅助性 T 细胞 17 型免疫反应,而急性特应性皮炎病变表现为辅助性 T 细胞 2 型占主导的炎症。目前基于单基因和信号通路的炎症性皮肤病模型并不完整。以前的工作使我们能够通过适当组合炎症细胞成分和破坏屏障功能,在皮肤人源化小鼠中模拟银屑病。在此,我们通过在去除部分角质层后,将人辅助性 T 细胞 2 淋巴细胞皮内注射到再生的人皮肤中,描述并表征了一种使用类似基于生物工程的方法的特应性皮炎动物模型。在这项工作中,我们广泛比较了这种模型与之前和改进的银屑病模型,在该模型中,辅助性 T 细胞 1 型和/或辅助性 T 细胞 17 型淋巴细胞替代外源性细胞因子。比较表达分析显示,在特定的表皮增殖和分化标志物以及免疫相关分子(包括抗菌肽)方面存在显著差异。同样,真皮炎症浸润的组成也存在重要差异。这些疾病准确可靠的动物模型的出现将有助于理解发病机制,并为药物开发和测试提供有价值的工具。

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