Abstract:
Lipids constitute a diverse class of molecular regulators with ubiquitous physiological roles in sustaining life. These carbon-rich compounds are primarily sourced from exogenous sources and may be used directly as structural cellular building blocks or as a substrate for generating signaling mediators to regulate cell behavior. In both of these roles, lipids play a key role in both immune activation and suppression, leading to inflammation and resolution, respectively. The simple yet elegant structural properties of lipids encompassing size, hydrophobicity, and molecular weight enable unique biodistribution profiles that facilitate preferential accumulation in target tissues to modulate relevant immune cell subsets. Thus, the structural and functional properties of lipids can be leveraged to generate new materials as pharmacological agents for potently modulating the immune system. Here, we discuss the properties of three classes of lipids: polyunsaturated fatty acids, short-chain fatty acids, and lipid adjuvants. We describe their immunoregulatory functions in modulating disease pathogenesis in preclinical models and in human clinical trials. We conclude with an outlook on harnessing the diverse and potent immune modulating properties of lipids for immunoregulation.
摘要:
脂质构成一类不同的分子调节剂,在维持生命中具有无处不在的生理作用。这些富含碳的化合物主要来源于外源来源,并且可以直接用作结构细胞结构单元或用作产生信号传导介质以调节细胞行为的底物。在这两个角色中,脂质在免疫激活和抑制中起关键作用,导致炎症和消退,分别。脂质的简单而优雅的结构特性包括大小,疏水性,和分子量实现了独特的生物分布曲线,其促进在靶组织中的优先积累以调节相关的免疫细胞亚群。因此,可以利用脂质的结构和功能特性来产生新的材料,作为有效调节免疫系统的药物。这里,我们讨论了三类脂质的性质:多不饱和脂肪酸,短链脂肪酸,和脂质佐剂。我们在临床前模型和人体临床试验中描述了它们在调节疾病发病机理中的免疫调节功能。最后,我们展望了利用脂质的多种有效免疫调节特性进行免疫调节的前景。