ArticleCell2021
Metabolic modeling of single Th17 cells reveals regulators of autoimmunity.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 319 papers.
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319 citing papers in PubMed, 474 citations in OpenAlex.
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259 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 11 institutions in 4 countries.
Allon WagnerDepartment of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Chao WangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: chao.wang@sri.utoronto.ca.
Johannes FesslerEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
David DeTomasoCenter for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Julian Avila-PachecoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
James KaminskiCenter for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sarah ZaghouaniEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Elena ChristianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Pratiksha ThakoreBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Brandon SchellhaassDepartment of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA.
Elliot Akama-GarrenEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Kerry PierceBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vasundhara SinghBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Noga Ron-HarelDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Biology, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
Vivian Paraskevi DouglasMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Lloyd BodEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Alexandra SchnellEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Daniel PulestonMax Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Raymond A SobelPalo Alto Veteran's Administration Health Care System and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marcia HaigisDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Erika L PearceMax Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Manoocher SoleimaniDepartment of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87121, USA.
Clary ClishBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
Vijay K KuchrooBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu.
Nir YosefDepartment of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: niryosef@berkeley.edu.
Broad Institute · USHarvard University · USUniversity of California, Berkeley · USBrigham and Women's Hospital · USMax Planck Institute of Immunobiology and Epigenetics · DEHoward Hughes Medical Institute · USMassachusetts Eye and Ear Infirmary · USStanford University · USTechnion – Israel Institute of Technology · ILUniversity of New Mexico · USUniversity of Toronto · CA
Funding
Tool and Technology Development CoreU19MH114821 · NIMH · COLD SPRING HARBOR LABORATORY · PI ARLOTTA, PAOLA, HUANG, Z JOSH · 2017 to 2021
$64.5MRole of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MTransgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5MTransgenic / Knock-out mouse coreP01AI073748 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI BEHAR, SAMUEL M · 2008 to 2019
$17.1MRole of Th1 specific cell surface molecule Tim-3 in EAE.R01NS045937 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 2003 to 2016
$4.9MT CELL RESPONSE TO MYELIN PROTEOLIPID PROTEINR01NS030843 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 1998 to 2019
$4.1MRole of Tim-3:Bat-3 pathway in inducing tolerogenic DCs and peripheral toleranceR01AI144166 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI VIJAY K. KUCHROO · 2020 to 2026
$3.2MNIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI056299NIAID NIH HHS P01 AI073748NIAID NIH HHS R01 AI144166NIMH NIH HHS U19 MH114821NINDS NIH HHS R01 NS030843NINDS NIH HHS R01 NS045937
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 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 vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T cells and attenuated tissue inflammation in CNS autoimmunity.
Indexed as
Models, BiologicalAcetyltransferasesAdenosine TriphosphateAerobiosisAlgorithmsAnimalsAutoimmunityChromatinCitric Acid CycleCytokinesDiamine N-AcetyltransferaseEflornithineEncephalomyelitis, Autoimmune, ExperimentalEpigenomeFatty AcidsGlycolysisAcetyltransferasesAdenosine TriphosphateChromatinCytokinesDiamine N-AcetyltransferaseEflornithineFatty AcidsJumonji Domain-Containing Histone DemethylasesKdm6b protein, mouseMitochondrial Membrane Transport ProteinsPutrescineDFMOexperimental autoimmune encephalomyelitisimmunometabolismin silico metabolic modelingmultiple sclerosispolyaminesputrescinesingle cell transcriptomicsspermidineT helper 17 cell
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