KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Anti-CD4 (RM4–5) | Thermo Fisher Scientific | Cat# 48–0042-80; RRID:AB_1272231 |
| Anti-CD4 (RM4–4, in vivo labeling) | BioLegend | Cat# 116006; RRID:AB_313691 |
| Anti-CD8α (53–6.7) | BioLegend | Cat# 100742; RRID:AB_2563056 |
| Anti-TCRβ (H57–597) | Thermo Fisher Scientific | Cat# 47–5961-82; RRID:AB_1272173 |
| Anti-CD44 (1M7) | BioLegend | Cat# 103047; RRID:AB_2562451 |
| Anti-CD62L (MEL-14) | Tonbo Biosciences | Cat# 60–0621; RRID:AB_469632 |
| Anti-CD69 (H1.2F3) | Thermo Fisher Scientific | Cat# 48–0691-82; RRID:AB_10719430 |
| Anti-PD-1 (J43) | Thermo Fisher Scientific | Cat# 17–9985-80; RRID:AB_11149860 |
| Anti-CD45.1 (A20) | BioLegend | Cat# 110736; RRID:AB_2562564 |
| Anti-CD45.2 (104) | Thermo Fisher Scientific | Cat# 48–0454-80; RRID:AB_11039533 |
| Anti-CD25 (PC61.5) | Thermo Fisher Scientific | Cat# 17–0251-82; RRID:AB_469366 |
| Anti-Foxp3 (FJK-16s) | Thermo Fisher Scientific | Cat# 12–5773-80; RRID:AB_465935 |
| Anti-Ki67 (SolA15) | Thermo Fisher Scientific | Cat# 25–5698-80; RRID:AB_11217689 |
| Anti-Bim (C34C5) | Cell Signaling Technology | Cat# 2933; RRID:AB_1030947 |
| Anti-GFP-Alexa Fluor 488 (FM264G) | BioLegend | Cat# 338008; RRID:AB_2563288 |
| Anti-IFN-γ (XMG1.2) | Thermo Fisher Scientific | Cat# 17–7311-81; RRID:AB_469503 |
| Anti-IL-4 (11B11) | Thermo Fisher Scientific | Cat# 12–7041-71; RRID:AB_466154 |
| Anti-IL-17 (eBio17B7) | Thermo Fisher Scientific | Cat# 45–7177-80; RRID:AB_925754 |
| Anti-CD3 (145–2C11) | Bio-X-Cell | Cat# BE0001; RRID:AB_2714218 |
| Anti-CD28 (37.51) | Bio-X-Cell | Cat# BE0015–1; RRID:AB_1107624 |
| Anti-β-actin (C4)-HRP | Santa Cruz Biotechnology | Cat# sc-47778 HRP; AB_2714189 |
| Anti-β-tubulin | Cell Signaling Technology | Cat# 2146, RRID:AB_2210545 |
| Anti-phospho-S6 (S235/236) (D57.2.2E) | Cell Signaling Technology | Cat# 4858; RRID:AB_916156 |
| Anti-phospho-4EBP1 (Thr37/46) (236B4) |
Cell Signaling Technology | Cat# 2855; RRID: AB_560835 |
| Anti-phospho-4EBP1 (Thr37/46) (236B4) -Alexa Fluor 647 conjugate |
Cell Signaling Technology | Cat# 5123 RRID: AB_2097838 |
| Anti-phospho-S6 (S235/236) (D57.2.2E)-Pacific Blue™ conjugate | Cell Signaling Technology | Cat# 8520, RRID:AB_2797646 |
| Anti-Mcl1 (LVUBKM) | Thermo Fisher Scientific | Cat# 12–9047-42, RRID:AB_2762598 |
| Anti-Bcl2 (BCL/10C4) | BioLegend | Cat# 633510, RRID:AB_2274702 |
| Anti-ICOS (7E.17G9) | Thermo Fisher Scientific | Cat# 12–9942-82, RRID:AB_466274 |
| Anti-CTLA4 (UC10–4B9) | BioLegend | Cat# 106312, RRID:AB_2563063 |
| Anti-KLRG1 (2F1) | BioLegend | Cat# 138419, RRID:AB_2563357 |
| Anti-CXCR3 (CXCR3–173) | BioLegend | Cat# 126531, RRID:AB_2563160 |
| Anti-CD73 (TY/11.8) | BioLegend | Cat# 127212, RRID:AB_11219190 |
| Anti-CD5 (53–7.3) | Thermo Fisher Scientific | Cat# 12–0051-81, RRID:AB_465522 |
| Anti-Bim (C34C5) | Cell Signaling Technology | Cat# 12186, RRID:AB_2797842 |
| Anti-Rap1A (C-17) | Santa Cruz Biotechnology | Cat# sc-1482, RRID:AB_2177124 |
| Anti-HDJ2 (KA2A5.6) | Lab Vision | Cat# MS-225-P0, RRID:AB_61951 |
| Anti-Rabbit IgG HRP conjugate | Promega | Cat# W4011, RRID:AB_430833 |
| Anti-Mouse IgG HRP conjugate | Promega | Cat# W4021, RRID:AB_430834 |
| Anti-Goat IgG HRP conjugate (sc-2345) | Santa Cruz Biotechnology | Cat# sc-2354, RRID:AB_628490 |
| Chemicals, Peptides, and Recombinant Proteins | ||
| 7-Aminoactinoymycin D (7AAD) | Sigma-Aldrich | Cat# A9400 |
| Simvastatin | Selleck Chemicals | Cat# S1792 |
| FTI-277 | Tocris | Cat# 2407 |
| GGTI-2147 | Sigma-Aldrich | Cat# 191102–87-1 |
| (+)-Mevalonolactone (dehydrated mevalonate) | Sigma-Aldrich | Cat# M4667–5G |
| Farnesyl pyrophosphate ammonium salt (FPP) | Sigma-Aldrich | Cat# 13058–04-3 |
| Geranylgeranyl pyrophosphate ammonium salt (GGPP) | Sigma-Aldrich | Cat# G6025 |
| Fixable Viability Dye eFluor™ 780 | Thermo Fisher Scientific | Cat# 65–0865-18 |
| Recombinant human IL-2 (in vitro stimulation) | R&D Systems | Cat# 202-IL |
| Phobol 12-myristate 13-acetate (PMA) | Sigma-Aldrich | Cat# P8139 |
| Ionomycin | Sigma-Aldrich | Cat# I0634 |
| Golgi-STOP | BD Biosciences | Cat# 554724 |
| Recombinant human IL-6 | National Cancer Institute | Cat# NSC720836 |
| Recombinant murine IL-3 | Thermo Fisher Scientific | Cat# PMC0034 |
| Recombinant murine stem-cell factor (SCF) | Thermo Fisher Scientific | Cat# PMC2115 |
| ABI probe: Pggt1b | Thermo Fisher Scientific | Mm01266356_m1 |
| ABI probe: Icos | Thermo Fisher Scientific | Mm00497600_m1 |
| ABI probe: Actb | Thermo Fisher Scientific | Mm00607939_s1 |
| Commercial Reagents | ||
| Foxp3 transcription factor staining buffer set | Thermo Fisher Scientific | Cat# 00–5523-00 |
| Cytofix/Cytoperm™ Fixation/Permeabilization Solution Kit | BD Biosciences | Cat# 554714 |
| CD4 (3LT4) Microbeads, mouse | Miltenyi Biotec | Cat# 130–117-043 |
| Lineage cell depletion kit | Miltenyi Biotec | Cat# 130–090-858 |
| Transfection reagent | Mirus | Cat# MIR2706 |
| 10× Perm/Wash Buffer | BD Biosciences | Cat# 554723 |
| Clariom S mouse array | Thermo Fisher Scientific | Cat# 902930 |
| BD Phosflow™ Fix Buffer I | BD Biosciences | Cat# 557870 |
| Phosflow™ Perm Buffer III | BD Biosciences | Cat# 558050 |
| CellTrace™ Violet Cell Proliferation Kit | Thermo Fisher Scientific | Ca# C34557 |
| Deposited Data | ||
| Fntb- or Pggt1b-deficient Treg-cell microarray data from mixed bone marrow chimeras | GEO (http://www.ncbi.nlm.nih.gov/geo/) | GSE158863 |
| In vitro cTreg-cell microarray data from DMSO, FTI, or GGTI treatments | GEO (http://www.ncbi.nlm.nih.gov/geo/) | GSE158863 |
| ATAC-Seq data | GEO (http://www.ncbi.nlm.nih.gov/geo/) | GSE158863 |
| Experimental Models: Cell Lines | ||
| Plat-E | Dr. Yun-Cai Liu, La Jolla Institute of Immunology | N/A |
| Experimental Models: Organisms/Strains | ||
| Mouse: C57BL/6J | The Jackson Laboratory | Cat# 000664; RRID:IMSR_JAX:000664 |
| Mouse: Fntbfl/fl | M. Bergo (Liu et al., 2010) | N/A |
| Mouse: Pggt1bfl/fl | M. Bergo (Khan et al., 2011) | N/A |
| Mouse: Hmgcrfl/fl | A. Waisman | N/A |
| Mouse: CD45.1+: B6.SJL-Ptprca Pep3b/BoyJ | The Jackson Laboratory | Cat# 002014; RRID:IMSR_JAX:002014 |
| Mouse: Cd4 Cre: Tg(Cd4-cre)1Cwi/BfluJ | The Jackson Laboratory | Cat# 017336; RRID:IMSR_JAX:017336 |
| Mouse: Rag1−/−: Rag1tm1Mom/J | The Jackson Laboratory | Cat# 002216; RRID:IMSR_JAX:002216 |
| Mouse: Foxp3YFP-Cre | A. Rudensky (Rubtsov et al., 2008) | N/A |
| Mouse: Rac1fl/fl | The Jackson Laboratory | Cat# JAX:005550, RRID:IMSR_JAX:005550 |
| Mouse: Rac2−/− | The Jackson Laboratory | Cat# JAX:004197, RRID:IMSR_JAX:004197 |
| Mouse: Tsc1−/− | The Jackson Laboratory | Cat# JAX:005680, RRID:IMSR_JAX:005680 |
| Mouse: C57BL/6-Tg(Nr4a1-EGFP/cre)820Khog/J (also known as Nur77-GFP) | The Jackson Laboratory | Cat# JAX:016617, RRID:IMSR_JAX:016617 |
| Mouse: C57BL/6-Foxp3tm1Flv/J (also known as Foxp3-RFP) | The Jackson Laboratory | Cat# JAX: 008374 RRID:IMSR JAX: 008374 |
| Oligonucleotides | ||
| Fntb-F: 5’-AACCGCTGTATAGTCTGAGACC-3’ | This paper | N/A |
| Fntb-R: 5’-TCTCCCTCTGCAAAATGAGCC-3’ | This paper | N/A |
| Hmgcr-F: 5’-AGCTTGCCCGAATTGTATGTG-3’ | (Zeng et al., 2013) | N/A |
| Hmgcr-R: 5’-TCTGTTGTGAACCATGTGACTTC-3’ | (Zeng et al., 2013) | N/A |
| Hmgcs1-F: 5’-AACTGGTGCAGAAATCTCTAGC-3’ | (Zeng et al., 2013) | N/A |
| Hmgcs1-R: 5’-GGTTGAATAGCTCAGAACTAGCC-3’ | (Zeng et al., 2013) | N/A |
| Fnta-F: 5’- CCCTATGGACGACGGGTTTC-3’ | This paper | N/A |
| Fnta-R:5’- TGATCTGGACCACTGGGTTAG-3’ | This paper | N/A |
| Actb-F: 5’-GACAGGATGCAGAAGGAGATTACTG-3’ | This paper | N/A |
| Actb-R: 5’-GCTGATCCACATCTGCTGGAA-3’ | This paper | N/A |
| Recombinant DNA | ||
| pCAG4-Eco | Addgene | Addgene plasmid # 12260 |
| pMX-GFP-Rac-G12V | (Shi et al., 2018) | Addgene Cat# 14567 |
| ICOS cDNA ORF Clone | Sino Biological | MG50466-M |
| Software and Algorithms | ||
| FlowJo v9.3 | FlowJo | https://www.flowjo.com/ |
| GraphPad Prism v6.0 | GraphPad | https://www.graphpad.com/scientific-software/prism/ |
| Other | ||
| LSR Fortessa flow cytometer | BD Biosciences | N/A |
| MoFlow cell sorter | Beckman-Coulter | N/A |
| Reflection cell sorter | iCyt | N/A |
| ODYSSEY Fc Analyzer | LI-COR | N/A |
| Gene set enrichment analysis (GSEA) software suite | (Subramanian et al., 2005) | http://www.broadinstitute.org/gsea/msigdb/ |