@article {1608578,
	title = {Metabolic modeling of single Th17 cells reveals regulators of autoimmunity},
	journal = {Cell},
	volume = {184},
	number = {16},
	year = {2021},
	month = {2021 Aug 05},
	pages = {4168-4185.e21},
	abstract = {Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T\&nbsp;cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In\&nbsp;vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T\&nbsp;cells and attenuated tissue inflammation in CNS autoimmunity.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2021.05.045},
	author = {Wagner, Allon and Wang, Chao and Fessler, Johannes and DeTomaso, David and Avila-Pacheco, Julian and Kaminski, James and Zaghouani, Sarah and Christian, Elena and Thakore, Pratiksha and Schellhaass, Brandon and Akama-Garren, Elliot and Pierce, Kerry and Singh, Vasundhara and Ron-Harel, Noga and Douglas, Vivian Paraskevi and Bod, Lloyd and Schnell, Alexandra and Puleston, Daniel and Sobel, Raymond A and Haigis, Marcia and Pearce, Erika L and Soleimani, Manoocher and Clish, Clary and Regev, Aviv and Kuchroo, Vijay K and Yosef, Nir}
}
