美国加州大学伯克利分校Nir Yosef等研究人员合作发现，Th17细胞的代谢重塑影响自身免疫。这一研究成果于2021年7月2日在线发表在国际学术期刊《细胞》上。
研究人员报道了Compass，这是一种基于单细胞RNA测序和通量平衡分析来表征细胞代谢状态的算法。研究人员应用Compass将代谢状态与辅助性T细胞17（Th17）功能变异性（致病潜力）相关联，并恢复了糖酵解和脂肪酸氧化之间的代谢转换，这类似于已知的Th17/调节性T细胞（Treg）差异，并通过代谢分析得以验证。Compass还预测了Th17的致病性与精氨酸和下游多胺代谢有关。
事实上，多胺相关酶的表达在致病性Th17中增强，而在Treg细胞中受到抑制。多胺代谢的化学和遗传扰动抑制了Th17细胞因子，促进了Foxp3的表达，并将Th17细胞的转录组和表观基因组重塑为Treg样状态。多胺途径的体内扰动改变了致脑炎T细胞的表型，并减轻了中枢神经系统自身免疫中的组织炎症。
据介绍，代谢是免疫细胞功能的主要调节器，但研究单个细胞的代谢状态仍然很困难。
附：英文原文
Title: Metabolic modeling of single Th17 cells reveals regulators of autoimmunity
Author: Allon Wagner, Chao Wang, Johannes Fessler, David DeTomaso, Julian Avila-Pacheco, James Kaminski, Sarah Zaghouani, Elena Christian, Pratiksha Thakore, Brandon Schellhaass, Elliot Akama-Garren, Kerry Pierce, Vasundhara Singh, Noga Ron-Harel, Vivian Paraskevi Douglas, Lloyd Bod, Alexandra Schnell, Daniel Puleston, Raymond A. Sobel, Marcia Haigis, Erika L. Pearce, Manoocher Soleimani, Clary Clish, Aviv Regev, Vijay K. Kuchroo, Nir Yosef
Issue&Volume: 2021-07-02
Abstract: Metabolism is a major regulator of immune cell function, but it remains difficultto study the metabolic status of individual cells. Here, we present Compass, an algorithmto characterize cellular metabolic states based on single-cell RNA sequencing andflux balance analysis. We applied Compass to associate metabolic states with T helper17 (Th17) functional variability (pathogenic potential) and recovered a metabolicswitch between glycolysis and fatty acid oxidation, akin to known Th17/regulatoryT cell (Treg) differences, which we validated by metabolic assays. Compass also predictedthat Th17 pathogenicity was associated with arginine and downstream polyamine metabolism.Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressedin Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibitedTh17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenomeof Th17 cells toward a Treg-like state. In vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenicT cells and attenuated tissue inflammation in CNS autoimmunity.
DOI: 10.1016/j.cell.2021.05.045
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00700-5