van Smeden Jeroen, Bouwstra Joke A
Curr Probl Dermatol. 2016;49:8-26. doi: 10.1159/000441540. Epub 2016 Feb 4.
Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to other skin diseases.
人体皮肤是身体与其环境之间的主要屏障。对于这种皮肤屏障功能至关重要的是皮肤最外层角质层（SC）中的脂质基质。其功能包括：（1）防止水分通过表皮过度流失；（2）避免环境中的化合物渗透到有活力的表皮和真皮层，从而引发免疫反应。SC脂质基质的组成主要由三类脂质主导：胆固醇、游离脂肪酸和神经酰胺。这些脂质呈现出高度有序的三维堆叠紧密排列脂质层结构（脂质片层）：即横向和片层脂质组织。这些脂质的排列方式取决于脂质的组成。一种非常常见的影响SC脂质屏障的皮肤病是特应性皮炎（AD）。本综述阐述了健康皮肤中SC脂质的组成和组织，并详细说明了AD患者皮损和非皮损皮肤中这些参数是如何变化的。关于脂质组成，讨论了三类主要脂质的变化以及脂质碳链长度的重要性。此外，本综述还探讨了这些脂质组成变化如何诱导脂质组织的变化，并随后与这些患者皮损和非皮损皮肤中受损的皮肤屏障功能相关联。此外，还批判性地讨论了丝聚合蛋白及其基因突变对SC脂质组成的影响。同时，还描述了丝聚合蛋白的分解产物、天然保湿因子分子及其与SC-pH的关系。最后，本文讨论了AD和其他相关皮肤病患者表皮脂质生物合成的一些主要变化，以及炎症如何对SC脂质和SC生物合成产生恶化作用。综述最后展望了与其他皮肤病相关的未来研究。
