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免疫在开发银屑病和特应性皮炎可靠动物模型中的重要性。

The importance of immunity in the development of reliable animal models for psoriasis and atopic dermatitis.

机构信息

Department of Bioengineering, Universidad Carlos III de Madrid, Leganés, 28911, Spain.

Hospital Fundación Jiménez Díaz e Instituto de Investigación FJD, Madrid, 28040, Spain.

出版信息

Immunol Cell Biol. 2020 Sep;98(8):626-638. doi: 10.1111/imcb.12365. Epub 2020 Jul 15.

Abstract

Psoriasis (PS) and atopic dermatitis (AD) are common inflammatory skin diseases characterized by an imbalance in specific T-cell subsets, resulting in a specific cytokine profile in patients. Obtaining models closely resembling both pathologies along with a relevant clinical impact is crucial for the development of new therapies because of the high prevalence of these diseases. Single-gene mouse models developed until now do not fully reflect the complexity of these disorders, in part not only because of inherent differences between mice and humans but also because of the multifactorial nature of these pathologies. The skin-humanized mouse model developed by our group, based on a tissue engineering approach, has been used to test therapeutic strategies, although this methodology is still technically challenging and not widely available. The skin-humanized mouse models for PS and AD reproduce human skin phenotypes, providing valuable tools for drug development and testing in the preclinical setting. The tissue engineering approach allows the development of personalized medicine, covering the broad genotypic spectrum of these pathologies. This review highlights the main differences between available murine models focusing on the tissue-specific immunity of PS and AD. We discuss their contribution to unravel the complex pathophysiology of these diseases and to translate this knowledge into more accurate therapies.

摘要

银屑病(PS)和特应性皮炎(AD)是常见的炎症性皮肤病,其特征是特定 T 细胞亚群失衡,导致患者产生特定的细胞因子谱。由于这些疾病的高患病率,获得与两种病理都非常相似的模型以及相关的临床影响对于新疗法的开发至关重要。迄今为止开发的单基因小鼠模型不能完全反映这些疾病的复杂性,部分原因不仅是由于老鼠和人类之间存在固有差异,还因为这些疾病具有多因素性质。我们小组基于组织工程方法开发的皮肤人源化小鼠模型已被用于测试治疗策略,尽管这种方法在技术上仍然具有挑战性,并且尚未广泛应用。用于 PS 和 AD 的皮肤人源化小鼠模型再现了人类皮肤表型,为药物开发和临床前测试提供了有价值的工具。组织工程方法允许开发个性化药物,涵盖这些疾病的广泛基因型谱。本综述重点介绍了现有小鼠模型之间的主要差异,重点关注 PS 和 AD 的组织特异性免疫。我们讨论了它们对揭示这些疾病复杂病理生理学的贡献,并将这些知识转化为更准确的治疗方法。

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