Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Dermatology and Department of Immunology, Cutaneous Biology Research Core, University of Pittsburgh, Pittsburgh, PA, USA.
Nat Immunol. 2018 Dec;19(12):1286-1298. doi: 10.1038/s41590-018-0256-2. Epub 2018 Nov 16.
The skin provides both a physical barrier and an immunologic barrier to external threats. The protective machinery of the skin has evolved to provide situation-specific responses to eliminate pathogens and to provide protection against physical dangers. Dysregulation of this machinery can give rise to the initiation and propagation of inflammatory loops in the epithelial microenvironment that result in inflammatory skin diseases in susceptible people. A defective barrier and microbial dysbiosis drive an interleukin 4 (IL-4) loop that underlies atopic dermatitis, while in psoriasis, disordered keratinocyte signaling and predisposition to type 17 responses drive a pathogenic IL-17 loop. Here we discuss the pathogenesis of atopic dermatitis and psoriasis in terms of the epithelial immune microenvironment-the microbiota, keratinocytes and sensory nerves-and the resulting inflammatory loops.
皮肤为人体提供了物理屏障和免疫屏障,以抵御外界威胁。皮肤的保护机制不断进化,以针对特定情况作出反应,消灭病原体并抵御物理危险。如果该机制失调,可能会引发上皮微环境中的炎症循环,使易感人群患上炎症性皮肤病。有缺陷的屏障和微生物失调会引发白细胞介素 4(IL-4)循环,导致特应性皮炎;而在银屑病中,角质形成细胞信号紊乱和 1 型 7 细胞反应倾向则会引发致病的白细胞介素 17(IL-17)循环。本文将从上皮免疫微环境(微生物群、角质形成细胞和感觉神经)及其引发的炎症循环的角度,讨论特应性皮炎和银屑病的发病机制。