O'Regan Grainne M, Irvine Alan D
Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):406-10. doi: 10.1097/ACI.0b013e32830e6fb2.
To provide a comprehensive summary of recent genetic advances as they relate to the pathogenesis of atopic dermatitis.
Atopic dermatitis is a common inflammatory skin disease with a complex cause, resulting from an elaborate interplay between environmental, immunological and genetic factors. The disease is often the prelude to an atopic diathesis that includes asthma and other allergic diseases. The identification of mutations in the barrier protein filaggrin as conferring major susceptibility to atopic dermatitis and atopic dermatitis related asthma has reconfigured our understanding of disease mechanisms and highlights the importance of epidermal barrier disruption as a primary event in the disease.
In this review we highlight recent advances in our understanding of how filaggrin might influence the environmental-immune interface, impacting disease penetrance, severity and trajectory, and the implications for both research and therapeutics in this field. Focusing on the downstream biological consequences of altered filaggrin expression and the sequence of immunological and environmental triggers that ensue will provide the rationale for targeted therapeutics capable of restoring or preventing disruption of barrier function.
全面总结近期与特应性皮炎发病机制相关的遗传学进展。
特应性皮炎是一种常见的炎症性皮肤病，病因复杂，是环境、免疫和遗传因素之间复杂相互作用的结果。该疾病通常是特应性素质（包括哮喘和其他过敏性疾病）的前奏。屏障蛋白丝聚合蛋白中的突变被确定为赋予特应性皮炎和特应性皮炎相关哮喘主要易感性，这重新构建了我们对疾病机制的理解，并突出了表皮屏障破坏作为该疾病主要事件的重要性。
在本综述中，我们强调了近期在理解丝聚合蛋白如何影响环境 - 免疫界面、影响疾病发生率、严重程度和病程方面取得的进展，以及对该领域研究和治疗的影响。关注丝聚合蛋白表达改变的下游生物学后果以及随之而来的免疫和环境触发序列，将为能够恢复或预防屏障功能破坏的靶向治疗提供理论依据。
