Lipid metabolism: a central modulator of RORγt-mediated Th17 cell differentiation.

IF 4.8 4区 医学 Q2 IMMUNOLOGY
Toshio Kanno, Keisuke Miyako, Yusuke Endo
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引用次数: 0

Abstract

Among the T helper cell subsets, Th17 cells contribute to the development of various inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Retinoid-related orphan receptor gamma t (RORγt), a nuclear hormone receptor, serves as a master transcription factor for Th17 cell differentiation. Recent findings have shown that modulating the metabolic pathway is critical for Th17 cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Suppression of lipid biosynthesis, either through the pharmacological inhibition or gene deletion of related enzymes in CD4+ T cells, results in significant impairment of Th17 cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic pathways have a pivotal role in the regulation of RORγt activity through the generation of endogenous RORγt lipid ligands. This review discusses recent discoveries highlighting the importance of lipid metabolism in Th17 cell differentiation and function, as well as exploring specific molecular pathways involved in RORγt activation through cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach to improve inflammatory and autoimmune disorders via the inhibition of RORγt.

脂质代谢:RORt 介导的 Th17 细胞分化的核心调节器。
在 T 辅助细胞亚群中,Th17 细胞是导致牛皮癣、类风湿性关节炎、炎症性肠病、类固醇耐药哮喘和多发性硬化症等各种炎症和自身免疫性疾病的病因。视黄醇相关孤儿受体γt(RORγt)是一种核激素受体,是 Th17 细胞分化的主转录因子。最近的研究结果表明,调节新陈代谢途径对 Th17 细胞的分化至关重要,特别是通过参与脂质的从头生物合成。通过药物抑制或基因缺失 CD4+ T 细胞中的相关酶来抑制脂质生物合成,会导致 Th17 细胞分化明显受损。机理研究表明,脂肪酸和胆固醇生物合成途径的代谢通量通过生成内源性 RORγt 脂质配体在调节 RORγt 活性方面起着关键作用。这篇综述讨论了最近的发现,强调了脂质代谢在 Th17 细胞分化和功能中的重要性,并探讨了通过细胞脂质代谢激活 RORγt 所涉及的特定分子途径。我们进一步阐述了通过抑制 RORγt 改善炎症和自身免疫性疾病的开创性治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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