Metabolism of murine TH17 cells: Impact on cell fate and function

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• 作者：Ran Wang and Laura A. Solt
• 关键词：Fatty acid HIF1 Glycolysis mTOR RORt TH17/Treg balance
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：46
• 期：4
• 页码：807-816
• 全文大小：277K
• ISSN：1521-4141

文摘

An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T-cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of T_H17 versus T regulatory (Treg) cells. T_H17 cells have garnered significant attention due to their roles in the pathology of immune-mediated inflammatory diseases. Attempts to characterize T_H17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the T_H17/Treg balance and present factors that mediate T_H17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1) promotion of glycolysis to favor T_H17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring T_H17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating T_H17-cell metabolism for the treatment of T_H17-mediated diseases.