Laboratory for Lipidomics and Lipid Biology, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK; Lydia Becker Institute of Immunology and Inflammation; Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Laboratory for Lipidomics and Lipid Biology, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Pharmacol Ther. 2024 Aug;260:108681. doi: 10.1016/j.pharmthera.2024.108681. Epub 2024 Jun 17.
Our skin protects us from external threats including ultraviolet radiation, pathogens and chemicals, and prevents excessive trans-epidermal water loss. These varied activities are reliant on a vast array of lipids, many of which are unique to skin, and that support physical, microbiological and immunological barriers. The cutaneous physical barrier is dependent on a specific lipid matrix that surrounds terminally-differentiated keratinocytes in the stratum corneum. Sebum- and keratinocyte-derived lipids cover the skin's surface and support and regulate the skin microbiota. Meanwhile, lipids signal between resident and infiltrating cutaneous immune cells, driving inflammation and its resolution in response to pathogens and other threats. Lipids of particular importance include ceramides, which are crucial for stratum corneum lipid matrix formation and therefore physical barrier functionality, fatty acids, which contribute to the acidic pH of the skin surface and regulate the microbiota, as well as the stratum corneum lipid matrix, and bioactive metabolites of these fatty acids, involved in cell signalling, inflammation, and numerous other cutaneous processes. These diverse and complex lipids maintain homeostasis in healthy skin, and are implicated in many cutaneous diseases, as well as unrelated systemic conditions with skin manifestations, and processes such as ageing. Lipids also contribute to the gut-skin axis, signalling between the two barrier sites. Therefore, skin lipids provide a valuable resource for exploration of healthy cutaneous processes, local and systemic disease development and progression, and accessible biomarker discovery for systemic disease, as well as an opportunity to fully understand the relationship between the host and the skin microbiota. Investigation of skin lipids could provide diagnostic and prognostic biomarkers, and help identify new targets for interventions. Development and improvement of existing in vitro and in silico approaches to explore the cutaneous lipidome, as well as advances in skin lipidomics technologies, will facilitate ongoing progress in skin lipid research.
我们的皮肤能保护我们免受外部威胁，包括紫外线辐射、病原体和化学物质，防止过多的经表皮水分流失。这些多样化的活动依赖于大量的脂质，其中许多脂质是皮肤所特有的，它们支持物理、微生物和免疫屏障。皮肤的物理屏障依赖于一个特定的脂质基质，这个基质环绕着角质形成细胞分化终末的角质层。皮脂和角质形成细胞衍生的脂质覆盖皮肤表面，并支持和调节皮肤微生物群。同时，脂质在驻留和浸润的皮肤免疫细胞之间传递信号，在应对病原体和其他威胁时，驱动炎症及其消退。特别重要的脂质包括神经酰胺，它对角质层脂质基质的形成至关重要，因此对物理屏障的功能至关重要；脂肪酸有助于皮肤表面的酸性 pH 值，并调节微生物群；还有角质层脂质基质和这些脂肪酸的生物活性代谢物，参与细胞信号转导、炎症和许多其他皮肤过程。这些多样化和复杂的脂质在健康的皮肤中维持着体内平衡，并且与许多皮肤疾病以及与皮肤表现相关的非相关系统性疾病以及衰老等过程有关。脂质也有助于肠-皮轴，在两个屏障部位之间传递信号。因此，皮肤脂质为探索健康的皮肤过程、局部和系统性疾病的发展和进展以及系统性疾病的可及生物标志物发现提供了有价值的资源，也为全面了解宿主与皮肤微生物群的关系提供了机会。对皮肤脂质的研究可以提供诊断和预后生物标志物，并有助于确定干预的新靶点。开发和改进现有的体外和计算方法来探索皮肤脂质组，以及皮肤脂质组学技术的进步，将有助于皮肤脂质研究的持续进展。
