KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Goat polyclonal anti-hamster IgG | MP Biomedicals | Cat#: 56984 |
| Hamster monoclonal anti-mouse CD3 | Bio X Cell | Cat#: BE0001-1; Clone 145-2C1 |
| Hamster monoclonal anti-mouse CD28 | Bio X Cell | Cat#: BE00015-1; Clone 37.51 |
| Hamster monoclonal anti-mouse IFN-gamma | Bio X Cell | Cat#: BE0055; Clone XMG1.2 |
| Rat monoclonal anti-mouse IL-4 | Bio X Cell | Cat#: BE0045; Clone 11B11 |
| Rat monoclonal anti-mouse CD16/CD32 | Bio X Cell | Cat#: BE0307; Clone 2.4G2 |
| Hamster monoclonal anti-mouse CD3 | BioLegend | Clone 145-2C11 |
| Rat monoclonal anti-mouse CD4 | BioLegend | Clone GK1.5 |
| Rat monoclonal anti-mouse CD8a | BioLegend | Clone 53-6.7 |
| Rat monoclonal anti-mouse CD11b | BioLegend | Clone M1/70 |
| Rat monoclonal anti-mouse CD45 | BioLegend | Clone 30-F11 |
| Rat monoclonal anti-mouse CD45RB | BioLegend | Clone C363-16A |
| Mouse monoclonal anti-mouse CD45.1 | BioLegend | Clone A20 |
| Rat monoclonal anti-mouse IL-17a | BioLegend | Clone C11-18H10.1 |
| Rat monoclonal anti-mouse IFN-gamma | BioLegend | Clone XMG1.2 |
| Rat monoclonal anti-mouse GM-CSF | BioLegend | Clone MP1-22E9 |
| Rat monoclonal anti-mouse TNF-alpha | BioLegend | Clone MP6-XT22 |
| Rat monoclonal anti-mouse IL-2 | BioLegend | Clone JES6-5H4 |
| Rat monoclonal anti-mouse Foxp3 | Thermo | Clone FJK-16s |
| Mouse monoclonal anti-mouse Tbet | BioLegend | Clone 4B10 |
| Rat monoclonal anti-mouse/human GATA3 | Thermo Fisher | Clone TWAJ |
| Mouse monoclonal anti-mouse RORgamma t | BD | Clone Q31-378 |
| Rat monoclonal anti-mouse CD25 | BioLegend | Clone PC61 |
| Mouse monoclonal anti-mouse Ki-67 | BD | Clone B56 |
| Rat monoclonal anti-mouse CD62L | BioLegend | Clone MEL-14 |
| Hamster monoclonal anti-mouse CD69 | BD | Clone H1.2F3 |
| Rat monoclonal anti-mouse CD44 | BioLegend | Clone IM7 |
| Rat monoclonal anti-mouse OX-40 | BioLegend | Clone OX-86 |
| Hamster monoclonal anti-mouse ICOS | BioLegend | Clone C398.4A |
| Rat monoclonal anti-mouse CD38 | BioLegend | Clone 90 |
| Rat monoclonal anti-mouse CD279 | BioLegend | Clone 29F.1A12 |
| Rat monoclonal anti-mouse CD98 | BioLegend | Clone 4F2 |
| Rat monoclonal anti-mouse CD71 | BioLegend | Clone RI7217 |
| Rat monoclonal anti-mouse CD11b | BioLegend | Clone M1/70 |
| anti-FcgRII/FcgRIII antibody | eBioscience | Clone 2.4G2 |
| Rabbit polyclonal anti-mouse acetyl-Histone H3 (Lys9/14) | Cell Signaling | Cat#: 9677 |
| Rabbit monoclonal anti-mouse acetyl-Histone H3 (Lys27) | Cell Signaling | Cat#: 8173; Clone D5E4 |
| Rabbit monoclonal anti-mouse H3K9me3 | Cell Signaling | Cat#:13969; Clone D4W1U |
| Rabbit monoclonal anti-mouse H3K27me3 | Cell Signaling | Cat#: 9733; Clone C36B11 |
| Rabbit polyclonal anti-mouse acetyl-Histone H3 (Lys9/14) | Diagenode | Cat#: C15410005 |
| Rabbit polyclonal anti-mouse acetyl-Histone H3 (Lys27) | Diagenode | Cat#: C15410174 |
| Isotype rabbit IgG | Cell Signaling | Cat#: 2729 |
| Mouse monoclonal anti-mouse/human/rat GLUT1 | Abcam | Cat#: ab40084; Clone SPM498 |
| Rabbit polyclonal anti-mouse/human IRF4 | Cell Signaling | Cat#: 4948S |
| Rabbit polyclonal anti-human GLUT3 | BioRad | Cat#: VPA00651 |
| Rabbit polyclonal anti-mouse/rat GLUT3 | Merck Millipore | Cat#: AB1344 |
| Mouse monoclonal anti-mouse/human/rat NFATc1 | Abcam | Cat#: ab2796; Clone 7A6 |
| Rabbit polyclonal anti-mouse/human/rat ACLY | Cell Signaling | Cat#: 4332 |
| Mouse monoclonal anti-mouse/human GAPDH | SCBT | Cat#: sc-3223; Clone 6C5 |
| Mouse monoclonal anti-mouse/human/rat beta-Actin-HRP | BioLegend | Cat#: 643807; Clone 2F1-1 |
| Mouse monoclonal anti-mouse/human/rat VDAC | Biolegend | Cat#: 820702; Clone N152B/23 |
| Goat polyclonal anti-mouse-HRP | Bio-Rad | Cat#: STAR207P |
| Goat anti-rabbit-HRP | Bio-Rad | Cat#: STAR208P |
| Rabbit polyclonal anti-human/mouse CD3 | Dako | Cat#: A0452 |
| Donkey polyclonal anti-rabbit IgG, Alexa Fluor 546 | Thermo Fisher | Cat#: A10040 |
| Rabbit monoclonal anti-human/mouse/rat/monkey TOM20 | CellSignalling | Cat#: D8T4N |
| Rabbit polyclonal anti-human Slc2a3 (GLUT3) | Sigma | Cat#:HPA006539 |
| Chemicals,Reagents, Peptides, and Recombinant Proteins | ||
| RPMI 1640 GlutaMAX | Gibco | Cat#: 61870-010 |
| RPMI 1640 w/o glucose | Roth | Cat#: 9094.1 |
| Penicillin-streptomycin | Gibco | Cat#: 15140122 |
| Puromycin | Gibco | Cat#:A1113802 |
| Plasticidin | Gibco | Cat#:A1113902 |
| 2-mercaptoethanol | Gibco | Cat#: 21985023 |
| FCS | Sigma | Cat#: 12133 |
| EDTA | Thermo | Cat#: 15575020 |
| HEPES | Gibco | Cat#: 11560496 |
| Bovine Serum Albumin (BSA) fatty acid free | Sigma | Cat#: A8806 |
| Seahorse XF RPMI medium, pH 7.4 | Agilent | Cat#: 103576-100 |
| Seahorse XF Calibrant Solution, pH 7.4 | Agilent | Cat#: 100840-000 |
| Prolong Gold Antifade Mounting Medium | Molecular Probes | Cat#: P10144 |
| Recombinant human TGF-beta | Peprotech | Cat#: 100-21 |
| Recombinant murine IL-6 | Peprotech | Cat#: 216-16 |
| Recombinant murine IL-1-beta | Peprotech | Cat#: AF-211-11B |
| Recombinant murine IL-12 p70 | Peprotech | Cat#: 210-12 |
| Recombinant human IL-2 | Peprotech | Cat#: 200-02 |
| Recombinant murine IL-4 | Peprotech | Cat#: AF-214-14 |
| Recombinant murine IL-23 | Invitrogen | Cat#: 14-8231-63 |
| Phorbol 12-myristate 13-acetate (PMA) | Sigma | Cat#: P8139-5MG |
| Ionomycin | Biomol | Cat#: AG-CN2-0418 |
| Brefeldin A | eBioscience | Cat#: 00-4506-51 |
| Monensin | eBioscience | Cat#: 00-4505-51 |
| Fixable Viability Dye eFluor 780 | eBioscience | Cat#: 65-0865-18 |
| Annexin A5 | BioLegend | Cat#: 640920 |
| 4’, 6-Diamidino-Phenylindole (DAPI) | Thermo | Cat#: D1306 |
| Propidium iodide (PI) | BioLegend | Cat#: 421301 |
| MitoTracker Deep Red | Invitrogen | Cat#: M22426 |
| Red Mitochondrial Superoxide Indicator (MitoSOX) | Invitrogen | Cat#: M36008 |
| Tetramethzlyrhodamine, Ethyl Ester, Percholorate (TMRE) | Invitrogen | Cat#: T669 |
| Trifluoromethoxy carbonylcyanide phenylhydrazone (Fccp) | Cayman Chemical | Cat#: Cay15218-50 |
| 4,4-Difluoro-1,3,5,7,8-Pentamethyl-4-Bora-3a,4a-Diaza-s-Indacene (BODIPY) | Invitrogen | Cat#: D3922 |
| 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) | Cayman Chemical | Cat#: Cay11046 |
| 123count eBeads Counting Beads | Invitrogen | 01-1234-42 |
| Permeabilization Buffer (10X) | eBioscience | Cat#: 00-8333-56 |
| IC Fixation Buffer | eBioscience | Cat#: 00-8222-49 |
| Foxp3/TF Staining Buffer | eBioscience | Cat#: 00-5523-00 |
| Oligomycine | Cayman Chemical | Cat#: Cay11341-5 |
| Rotenone | AdipoGen Life Sciences | Cat#: AG-CN2-0516-G001 |
| Antimycin A | Sigma | Cat#: A8674 |
| 2-Deoxy-D-glucose (2-DG) | Sigma | Cat#: D8375 |
| Cell-Tak | Corning | Cat#: 354240 |
| L-Glutamine | Gibco | Cat#: 25030081 |
| D-Glucose | Sigma | Cat#: G7021 |
| Sodium Pyruvate | Sigma | Cat#: P2256-5G |
| Formaldehyde 16%, methanol-free | ThermoFischer | Cat#: 28906 |
| Luxol Fast Blue (Solvent Blue) | Roth | Cat#: 7709.1 |
| Cresyl Violet | Sigma | Cat#: C5042 |
| MOG35-55 peptide | Synpeptide | Cat#: MOG35-55 |
| Pertussis Toxin | Enzo | Cat#: BML-G100 |
| Mycobacterium tuberculosis H37Ra | FisherScientific | Cat#: 10218823 |
| Incomplete Freund’s Adjuvant | BD | Cat#: 263910 |
| Phenol-Chloroform-Isoamylalkohole | Roth | Cat#: A156.1 |
| Potassium Hydroxycitrate Tribasic Monohydrate (2-HC) | Sigma | Cat#: 59847 |
| Sodium Acetate | Sigma | Cat#: S5636 |
| Sodium Lactate | Sigma | Cat#: 71718 |
| Palmitic Acid | Sigma | Cat#: P0500-10G |
| Sodium Oleate | Sigma | Cat#: O7501-250mg |
| Soraphen A | Rolf Möller | Berod, Friedrich et al. 2014 |
| 5-Tetradecyloxy-2-furonic acid (TOFA) | Sigma | Cat#: T6575-5MG |
| 2-Oxoglutarsäure-dimethylester (DMK) | Sigma | Cat#: 349631 |
| Polybrene | SantaCruz | Cat#: sc-134220 |
| GeneJet Tranfection reagent | Thermo Fisher | Cat#: SL100488 |
| Collagenase D | Roche | Cat#: 11088858001 |
| DNase 1 | Thermo Fisher | Cat#: EN0521 |
| Dispase | BD | Cat#: 354235 |
| RIPA lysis buffer | SantaCruz | Cat#: sc-24948 |
| complete Mini, EDTA-free | Roche | Cat#: 11836170001 |
| ROTI Load 1 | Roth | Cat#: K929.1 |
| RNase A | Thermo Scientific | Cat#: EN0531 |
| Proteinase K | Thermo Scientific | Cat#: EO0491 |
| [3H] 2-Deoxy-D-glucose | Perkin Elmer | Cat#: NET328A250UC |
| ROTISZINT®eco plus LSC-universal cocktail | Roth | Cat#: 0016.3 |
| [14C(U)]-D-glucose | Hartman Analytic | Cat#: 20562910 |
| Critical Commercial Assays | ||
| MojoSortTM Mouse CD4 T Cell Isolation Kit | BioLegend | Cat#: 480033 |
| CellTrace Violet Cell Proliferation Kit | Invitrogen | Cat#: C34557 |
| Acetyl-Coenzym A Assay Kit | Sigma | Cat#: MAK039-1KT |
| Seahorse Xfe FluxPak | Agilent | Cat#: 102601-100 |
| Pierce 660nm Protein Assay | Thermo Fisher | Cat#: 22662 |
| Protein A/G Magnetic Beads | Pierce | Cat#: 88802 |
| RNeasy Plus Micro Kit | Quiagen | Cat#: 74034 |
| RNAprotect Cell Reagent | Quiagen | Cat#: 76526 |
| Roti-Prep RNA Mini | Roth | Cat#: 8485.2 |
| iScript cDNA Synthesis Kit | Bio-Rad | Cat#: 1708891 |
| iTaq Universal SYBR Green Supermix | Bio-Rad | Cat#: 1725124 |
| CHIP DNA Clean & Concentrator Kit | Zymo | Cat#: D5205 |
| Deposited Data | ||
| Data S1 | This study | |
| RNA-seq data 1; Th1 and Th17 cells differentiated from WT and Slc2a3fl/flCd4Cre mice | This study | GSE192659 |
| RNA-seq data 2; Th17 cells differentiated from WT, Slc2a3fl/flCd4Cre and Aclyfl/flCd4Cre mice with and without 10 mM acetate treatment | This study | GSE192663 |
| ChIP-seq data (H3 K9/14ac) | This study | GSE193515 |
| ChIP-seq data (NFATc1) | Klein Hessling et al. 2017 | GSE98726 |
| ChIP-seq data (STAT3) | Hirahara et al 2015 | GSE65621 |
| ChIP-seq data (HIF-1a) | Ciofani et al 2012 | GSE40918 |
| ChIP-seq data (IRF4) | Man et al 2013 | GSE49931 |
| ChIP-seq data (NFATc2) | Martinez et al 2015 | GSE64409 |
| DNaseI-seq data | Bevington et al 2016 | GSE67465 |
| ATAC-seq data | Mognol et al 2017 | GSE88987 |
| ATAC-seq data | Qui et al 2020 | GSE127768 |
| Experimental Models: Cell Lines/bacteria/viruses | ||
| Platinum-E retroviral packaging cell line | Cell Biolabs Inc. | Cat# RV-101 |
| Citrobacter rodentium (strain ICC180) | Friedrich et al. 2017 | N/A |
| LCMV (Armstrong strain) | Vaeth et al. 2017 | N/A |
| Experimental Models: Mouse Strain | ||
| Mouse: Cd4Cre | Jackson Laboratories | Cat#: 017336 |
| Mouse: Slc2a3fl/fl | Provided by E. Dale Abel (Iowa) | Trevor P. Fidler et al., 2017 |
| Mouse: Aclyfl/fl | Jackson Laboratories | Cat#: 43555-JAX |
| Mouse: Irf4fl/fl | Jackson Laboratories | Cat#: 009380 |
| Mouse: Stat3fl/fl | Jackson Laboratories | Cat#: 016923 |
| Mouse: Cd28−/− | Jackson Laboratories | Cat#: 002666 |
| Mouse: Hif1afl/fl | Jackson Laboratories | Cat#: 007561 |
| Mouse: Rag2−/−γc−/− | Jackson Laboratories | Cat#: 014593 |
| Mouse: Rag1−/− | Jackson Laboratories | Cat#: 002216 |
| Mouse: Rosa26LSL-Cas9 | Jackson Laboratories | Cat#: 026175 |
| Mouse: CD45.1+ C57BL/6 | Jackson Laboratories | Cat#: 002014 |
| Oligonucleotides | ||
| See Table S1 for gRNAs | Sigma | This study |
| See Table S2 for primers for qRT-PCR | Sigma | This study |
| See Table S3 for primers for ChIP-qPCR | Sigma | This study |
| Recombinant DNA | ||
| pMIG | Addgene | Cat#: 9044 |
| pMIG-GLUT3 | This study | N/A |
| retro-gRNA-eGFP | Addgene | Cat#: 116926 |
| retro-gAcly-eGFP | This study | N/A |
| Software and Algorithms | ||
| FACSDiva | BD Bioscience | N/A |
| FlowJo software (Tree Star, Inc.) | FlowJo LLC | https://www.flowjo.com/ |
| GraphPad Prism V9 | GraphPad Software | https://www.graphpad.com/ |
| MetaboAnalyst 4.0 | Xia Lab, McGill University | https://www.metaboanalyst.ca |
| Illustrator CS5 | Adobe Systems Inc. | https://www.adobe.com/de/creativecloud/membership.html |
| Integrative Genome Viewer (IGV) | Broad Institute | https://software.broadinstitute.org/software/igv/ |
| LCS software | Leica | N/A |
| ImageJ | NIH | N/A |
| Icy | Institut Pasteur, France BioImaging | http://icy.bioimageanalysis.org |
| Xcalibur software | Thermo Scientific | https://www.thermofisher.com/order/catalog/product/OPTON-30965#/OPTON-30965 |
| ChopChop | Labun et al., 2019 | https://chopchop.cbu.uib.no |
| Other | ||
| XFe96 Extracellular Flux Analyzer | Seahorse Bioscience | N/A |
| ChemiDoc imaging system | BioRad | N/A |
| DMi8 automated laser-scanning confocal microscope | Leica | N/A |
| FlexStation 3 multi-mode microplate reader | Molecular Devices | N/A |
| Celesta Flow Cytometer | BD Bioscience | N/A |
| Aurora Flow Cytometer | Cytek | N/A |
| Biorupter Plus Sonication System | Diagenode | N/A |
| E220 sonicator | Covaris | N/A |
| Dionex UltiMate 3000 LC System | Thermo Scientific | N/A |
| Q Exactive Orbitrap mass spectrometer | Thermo Scientific | N/A |
| SX-8G Compact IP-Star | Diagenode | N/A |
| NovaSeq Illumina sequencer | Illumina | N/A |
| BD FACSAria III cell sorter | BD | N/A |
| QubitTM 3.0 Fluometer | Thermo Scientific | N/A |
| 2100 Bioanalyzer | Agilent | N/A |
| NextSeq 500 platform | Illumina | N/A |