肉芽肿形成过程中的代谢重编程和巨噬细胞极化

IF 4.8 4区 医学 Q2 IMMUNOLOGY
Satoshi Nakamizo, Kenji Kabashima
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引用次数: 0

摘要

这篇综述文章深入探讨了肉芽肿形成的复杂性,重点是这些免疫结构内部的新陈代谢重编程,尤其是在结核病和肉样瘤病中。文章强调了单核-巨噬细胞系在肉芽肿形成和维持中的作用,强调了这些细胞对环境线索和炎症刺激的适应性。讨论的关键是受各种细胞因子影响的巨噬细胞极化,详细探讨了在缺氧条件下向糖酵解的代谢转变,以及利用磷酸戊糖途径(PPP)进行关键的生物合成过程。其中特别关注巨噬细胞中 L-精氨酸的代谢及其对免疫反应和肉芽肿功能的影响。综述还强调了雷帕霉素机械靶标(mTOR)信号在巨噬细胞分化中的作用及其对肉芽肿疾病的影响。肉芽肿相关巨噬细胞中 PPP 活性的升高以及 NADPH 对氧化应激的保护作用等发现为肉芽肿生物学提供了新的见解。综述最后提出了在这些代谢途径中调节肉芽肿形成和功能的潜在治疗靶点,为以慢性炎症和肉芽肿形成为特征的疾病提出了新的治疗途径。这项工作极大地促进了人们对免疫调节和慢性炎症的理解,为肉芽肿疾病的未来研究和治疗提供了途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolic reprogramming and macrophage polarization in granuloma formation.

This review article delves into the complexities of granuloma formation, focusing on the metabolic reprogramming within these immune structures, especially in tuberculosis and sarcoidosis. It underscores the role of the monocyte-macrophage lineage in granuloma formation and maintenance, emphasizing the adaptability of these cells to environmental cues and inflammatory stimuli. Key to the discussion is the macrophage polarization influenced by various cytokines, with a detailed exploration of the metabolic shifts towards glycolysis under hypoxic conditions and the utilization of the pentose phosphate pathway (PPP) for crucial biosynthetic processes. Significant attention is given to the metabolism of L-arginine in macrophages and its impact on immune response and granuloma function. The review also highlights the role of mechanistic target of rapamycin (mTOR) signaling in macrophage differentiation and its implications in granulomatous diseases. Discoveries such as elevated PPP activity in granuloma-associated macrophages and the protective role of NADPH against oxidative stress offer novel insights into granuloma biology. The review concludes by suggesting potential therapeutic targets within these metabolic pathways to modulate granuloma formation and function, proposing new treatment avenues for conditions characterized by chronic inflammation and granuloma formation. This work contributes significantly to the understanding of immune regulation and chronic inflammation, presenting avenues for future research and therapy in granulomatous diseases.

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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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