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靶向肾脏疾病中的免疫细胞代谢。

Targeting immune cell metabolism in kidney diseases.

机构信息

Laboratory of Immunobiology of Transplantation, Department of Immunology, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

Center for Natural and Human Sciences, Universidade Federal do ABC, Santo André, São Paulo, Brazil.

出版信息

Nat Rev Nephrol. 2021 Jul;17(7):465-480. doi: 10.1038/s41581-021-00413-7. Epub 2021 Apr 7.

Abstract

Insights into the relationship between immunometabolism and inflammation have enabled the targeting of several immunity-mediated inflammatory processes that underlie infectious diseases and cancer or drive transplant rejection, but this field remains largely unexplored in kidney diseases. The kidneys comprise heterogeneous cell populations, contain distinct microenvironments such as areas of hypoxia and hypersalinity, and are responsible for a functional triad of filtration, reabsorption and secretion. These distinctive features create myriad potential metabolic therapeutic targets in the kidney. Immune cells have crucial roles in the maintenance of kidney homeostasis and in the response to kidney injury, and their function is intricately connected to their metabolic properties. Changes in nutrient availability and biomolecules, such as cytokines, growth factors and hormones, initiate cellular signalling events that involve energy-sensing molecules and other metabolism-related proteins to coordinate immune cell differentiation, activation and function. Disruption of homeostasis promptly triggers the metabolic reorganization of kidney immune and non-immune cells, which can promote inflammation and tissue damage. The metabolic differences between kidney and immune cells offer an opportunity to specifically target immunometabolism in the kidney.

摘要

对免疫代谢和炎症之间关系的深入了解,使人们能够针对几种感染性疾病和癌症的免疫介导的炎症过程,或导致移植排斥的过程进行靶向治疗,但这一领域在肾脏疾病中基本上仍未得到探索。肾脏包含异质细胞群体,包含缺氧和高渗等独特的微环境,并且负责过滤、重吸收和分泌的功能三联体。这些独特的特征在肾脏中创造了无数潜在的代谢治疗靶点。免疫细胞在维持肾脏内环境稳定和对肾脏损伤的反应中起着至关重要的作用,它们的功能与其代谢特性密切相关。营养物质和生物分子(如细胞因子、生长因子和激素)的变化会引发细胞信号事件,涉及能量感应分子和其他与代谢相关的蛋白质,以协调免疫细胞的分化、激活和功能。内稳态的破坏会迅速引发肾脏免疫和非免疫细胞的代谢重排,从而促进炎症和组织损伤。肾脏和免疫细胞之间的代谢差异为肾脏中的免疫代谢提供了一个特定的靶向机会。

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