How lipid mediators promote the resolution of inflammatory skin disease

脂质介质如何促进炎症性皮肤病的消退

• 批准号: 2775646
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2775646
• 关键词: How; lipid; mediators; promote; resolution

The skin is a crucial barrier between the environment and the internal body, and as such it is home to a plethora of immune cells ready to respond to invading pathogens. However, these cells must remain tolerant to harmless environmental substances and commensal microbes. Therefore, the activity of skin immune cells must be tightly regulated to prevent inappropriate activation and subsequent inflammation. In recent years it has become clear that this regulation is not passive, but is actively maintained by regulatory mechanisms including cell surface receptors, cell-cell interactions and the secretion of regulatory molecules. Dysregulation of these regulatory mechanisms leads to chronic inflammation, such as that seen in the chronic inflammatory skin diseases, psoriasis and atopic dermatitis (eczema). Whilst the involvement of proteins in this active regulation of inflammation has been studied, the involvement of lipid mediators remains a relatively unexplored area of research. This is despite the skin being a highly lipid rich tissue. This project will profile the bioactive lipid mediators present in skin throughout the induction, peak and resolution of inflammatory responses, to identify signalling lipids involved in regulating inflammation. The mechanisms by which these lipids regulate inflammation will be determined using in vitro and in vivo immune cell activity assays, and the potential to manipulate these lipids to suppress inflammation will be examined. This project will provide training in key techniques such as pre-clinical models of inflammatory disease (psoriasis and atopic dermatitis), flow cytometry, cell culture and immunological assays, ELISA, QPCR and lipidomic analysis by mass spectrometry. This project will identify novel regulation of immune cell activity by bioactive lipids. These findings will pave the way for novel therapeutic strategies for the treatment of psoriasis and atopic dermatitis, which are highly prevalent inflammatory skin diseases, for which there is currently no cure. These regulatory lipid mediators may also be dysregulated in inflammatory diseases affecting tissues other than skin, so this research may have wide ranging impacts on our understanding of inflammatory disease.

皮肤是环境与内部身体之间的关键障碍，因此，它是许多可以应对入侵病原体反应的免疫细胞的家园。但是，这些细胞必须保持对无害环境物质和共生微生物的耐受性。因此，必须严格调节皮肤免疫细胞的活性，以防止不适当的激活和随后的炎症。近年来，很明显，这种调节不是被动的，而是通过包括细胞表面受体，细胞 - 细胞相互作用和调节分子的分泌的调节机制积极维持的。这些调节机制的失调会导致慢性炎症，例如在慢性炎性皮肤病，牛皮癣和特应性皮炎（湿疹）中看到的。尽管已经研究了蛋白质参与这种主动调节炎症的研究，但脂质介质的参与仍然是相对未开发的研究领域。尽管皮肤是高度脂质的组织，但这仍然是。该项目将在整个诱导过程中，炎症反应的峰值和分辨率，介绍皮肤中存在的生物活性脂质介质，以鉴定与调节炎症有关的信号传导脂质。这些脂质将使用体外和体内免疫细胞活性分析确定调节炎症的机制，并检查操纵这些脂质以抑制炎症的潜力。该项目将提供关键技术的培训，例如炎症性疾病的临床前模型（牛皮癣和特应性皮炎），流式细胞仪，细胞培养和免疫学测定，ELISA，qPCR和脂质分析，质量光谱法分析。该项目将通过生物活性脂质确定对免疫细胞活性的新调节。这些发现将为牛皮癣和特应性皮炎治疗的新型治疗策略铺平道路，这些治疗是高度普遍的炎性皮肤病，目前尚无治愈方法。这些调节性脂质介质在影响皮肤以外的组织以外的炎症性疾病中也可能失调，因此这项研究可能对我们对炎症性疾病的理解产生广泛的影响。