The diverse distribution and functions of regulatory T cells (Tregs) ensure tissue and immune homeostasis; however, it remains unclear which factors can guide distribution, local differentiation, and tissue context-specific behavior in Tregs. Although the emerging concept that Tregs could re-adjust their transcriptome based on their habitations is supported by recent findings, the underlying mechanisms that reprogram transcriptome in Tregs are unknown. In the past decade, metabolic machineries have been revealed as a new regulatory circuit, known as immunometabolic regulation, to orchestrate activation, differentiation, and functions in a variety of immune cells, including Tregs. Given that systemic and local alterations of nutrient availability and metabolite profile associate with perturbation of Treg abundance and functions, it highlights that immunometabolic regulation may be one of the mechanisms that orchestrate tissue context-specific regulation in Tregs. The understanding on how metabolic program instructs Tregs in peripheral tissues not only represents a critical opportunity to delineate a new avenue in Treg biology but also provides a unique window to harness Treg-targeting approaches for treating cancer and autoimmunity with minimizing side effects. This review will highlight the metabolic features on guiding Treg formation and function in a disease-oriented perspective and aim to pave the foundation for future studies.

中文翻译：

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代谢适应在调节性T细胞中协调组织情境依赖性行为。

调节性T细胞（Tregs）的多样化分布和功能可确保组织和免疫稳态。然而，目前尚不清楚哪些因素可以指导Tregs的分布，局部分化和组织背景特异性行为。尽管最近的发现支持了新的概念，即Treg可以根据其居住环境重新调节转录组，但目前尚不清楚在Treg中重新编程转录组的潜在机制。在过去的十年中，代谢机制已被揭示为一种新的调节回路，称为免疫代谢调节，以协调各种免疫细胞（包括Treg）的激活，分化和功能。鉴于营养素利用率和代谢产物分布的系统和局部变化与Treg丰度和功能的扰动相关，它强调免疫代谢调节可能是在Tregs中组织组织特定于环境的调节的机制之一。对代谢程序如何指导周围组织中Treg的理解，不仅是描绘Treg生物学新途径的关键机会，而且还为利用Treg靶向方法治疗癌症和自身免疫性并将副作用减至最小提供了独特的窗口。这篇综述将以疾病为导向，着重于指导Treg形成和功能的代谢特征，并为将来的研究奠定基础。对代谢程序如何指导周围组织中Treg的理解，不仅是描绘Treg生物学新途径的关键机会，而且还为利用Treg靶向方法治疗癌症和自身免疫性并将副作用减至最小提供了独特的窗口。这篇综述将以疾病为导向，着重于指导Treg形成和功能的代谢特征，并为将来的研究奠定基础。对代谢程序如何指导周围组织中Treg的理解，不仅是描绘Treg生物学新途径的关键机会，而且还为利用Treg靶向方法治疗癌症和自身免疫性并将副作用减至最小提供了独特的窗口。这篇综述将以疾病为导向，着重于指导Treg形成和功能的代谢特征，并为将来的研究奠定基础。