Metabolism plays a crucial role in regulating the function of immune cells in both health and disease, with altered metabolism contributing to the pathogenesis of cancer and many inflammatory diseases. The local microenvironment has a profound impact on the metabolism of immune cells. Therefore, immunological and metabolic heterogeneity as well as the spatial organization of cells in tissues should be taken into account when studying immunometabolism. Here, we highlight challenges of investigating metabolic communication. Additionally, we review the capabilities and limitations of current technologies for studying metabolism in inflamed microenvironments, including single-cell omics techniques, flow cytometry-based methods (Met-Flow, single-cell energetic metabolism by profiling translation inhibition (SCENITH)), cytometry by time of flight (CyTOF), cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq), and mass spectrometry imaging. Considering the importance of metabolism in regulating immune cells in diseased states, we also discuss the applications of metabolomics in clinical research, as well as some hurdles to overcome to implement these techniques in standard clinical practice. Finally, we provide a flowchart to assist scientists in designing effective strategies to unravel immunometabolism in disease-relevant contexts.

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破译代谢串扰的背景：炎症性疾病的教训

代谢在健康和疾病中调节免疫细胞的功能中发挥着至关重要的作用，代谢的改变导致癌症和许多炎症性疾病的发病机制。局部微环境对免疫细胞的代谢有着深远的影响。因此，在研究免疫代谢时，应考虑免疫和代谢异质性以及组织中细胞的空间组织。在这里，我们强调研究代谢通讯的挑战。此外，我们回顾了当前研究炎症微环境中代谢的技术的能力和局限性，包括单细胞组学技术、基于流式细胞术的方法（Met-Flow、通过分析翻译抑制进行单细胞能量代谢（SCENITH））、细胞计数通过飞行时间 (CyTOF)、通过测序 (CITE-Seq) 和质谱成像对转录组和表位进行细胞索引。考虑到代谢在调节疾病状态下的免疫细胞中的重要性，我们还讨论了代谢组学在临床研究中的应用，以及在标准临床实践中实施这些技术需要克服的一些障碍。最后，我们提供了一个流程图，帮助科学家设计有效的策略来阐明疾病相关背景下的免疫代谢。