How does polyunsaturated fatty acid biosynthesis regulate T-lymphocyte function?
How does polyunsaturated fatty acid biosynthesis regulate T-lymphocyte function?
复制标题
多不饱和脂肪酸生物合成如何调节T淋巴细胞功能？
DOI：
10.1111/nbu.12404
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发表时间：
2019
影响因子：
3.3
通讯作者：
Fielding B
中科院分区：
文献类型：
--
作者：
Fielding B
以慢性炎症和保护性免疫反应下降为特征的免疫功能调节受损是健康老龄化的主要挑战。因此，了解调节免疫功能的机制以及衰老对此类过程的影响非常重要。免疫反应的适当诱导和解决需要有足够的多不饱和脂肪酸 (PUFA) 来掺入细胞膜。然而，人类无法从头合成 PUFA，并且依赖于预先形成的 PUFA 的饮食摄入量或肝脏从必需脂肪酸、亚油酸 (LA，18:2n-6) 和 α-亚麻酸 (aLNA，18:3n-3) 的合成。我们已经证明，外周血单核细胞的激活通过一种涉及改变该途径中关键基因的表观遗传调控的机制，增加了必需脂肪酸的 PUFA 生物合成。此外，PUFA合成的诱导直接参与淋巴细胞活化和增殖的调节。本文“多不饱和脂肪酸生物合成如何调节 T 淋巴细胞功能？”中描述的生物技术和生物科学研究理事会响应模式奖的目的是确定 PUFA 生物合成如何调节 T 细胞功能以及衰老对此过程的影响。该项目将确定生物合成途径中的调节点以及这些调节点如何影响老年人中 PUFA 合成的上调能力。我们将使用 LA 和 aLNA 的稳定同位素示踪剂来确定新合成的 PUFA 是否是脂质介质合成的优先底物以及它们是否参与介导细胞信号传导的膜微域的形成。
Impaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response require adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAsde novoand are dependent upon dietary intake for pre‐formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n‐6) and alpha‐linolenic acid (aLNA, 18:3n‐3). We have shown that activation of peripheral blood mononuclear cells increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the Biotechnology and Biological Sciences Research Council responsive mode award described in this paper, ‘How does polyunsaturated fatty acid biosynthesis regulate T‐lymphocyte function?’, is to determine how PUFA biosynthesis regulates T‐cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up‐regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling.