Immuno-metabolic reprogramming of T cell: a new frontier for pharmacotherapy of Rheumatoid arthritis

References

• Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023–2038. doi: 10.1016/S0140-6736(16)30173-8.
   Google Scholar
• Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4(Suppl 3):S265–S272. doi: 10.1186/ar578.
   Google Scholar
• Lin YJ, Anzaghe M, Schülke S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells. 2020;9:880. doi: 10.3390/cells9040880.
   Google Scholar
• Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. Lancet. 2010;376:1094–1108. doi: 10.1016/S0140-6736(10)60826-4.
   Google Scholar
• LaRosa DF, Orange JS. 1. Lymphocytes. JACI. 2008;121(2):S364–S369. doi: 10.1016/j.jaci.2007.06.016.
   PubMed Web of Science ®Google Scholar
• Yan F, Mo X, Liu J, et al. Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (review). Mol Med Rep. 2017;16(5):7175–7184. doi: 10.3892/mmr.2017.7525.
   PubMed Web of Science ®Google Scholar
• Mousset CM, Hobo W, Woestenenk R, et al. Comprehensive phenotyping of T cells using flow cytometry. Cytometry A. 2019;95(6):647–654. doi: 10.1002/cyto.a.23724.
   Google Scholar
• Kumar B v, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity. 2018;48(2):202–213. doi: 10.1016/j.immuni.2018.01.007.
   Google Scholar
• Wan YY. Multi-tasking of helper T cells. Immunology. 2010;130(2):166–171. doi: 10.1111/j.1365-2567.2010.03289.x.
   PubMed Web of Science ®Google Scholar
• Brummelman J, Pilipow K, Lugli E. The single-cell phenotypic identity of human CD8 + and CD4 + T cells. Int Rev Cell Mol Biol. 2018;341:63–124. doi: 10.1016/bs.ircmb.2018.05.007.
   PubMed Web of Science ®Google Scholar
• Schmitt N, Ueno H. Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol. 2015;34:130–136. doi: 10.1016/j.coi.2015.03.007.
   PubMed Web of Science ®Google Scholar
• Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015;75:14–24. doi: 10.1016/j.cyto.2015.05.010.
   Google Scholar
• Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol. 2002;2(12):933–944. doi: 10.1038/nri954.
   PubMed Web of Science ®Google Scholar
• Zhu J. T helper cell differentiation, heterogeneity, and plasticity. Cold Spring Harb Perspect Biol. 2018;10(10):a030338. doi: 10.1101/cshperspect.a030338.
   PubMed Web of Science ®Google Scholar
• Evans CM, Jenner RG. Transcription factor interplay in t helper cell differentiation. Brief Funct Genomics. 2013;12(6):499–511. doi: 10.1093/bfgp/elt025.
   PubMed Web of Science ®Google Scholar
• Agnello D, Lankford CSR, Bream J, et al. Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights. J Clin Immunol. 2003;23(3):147–161. doi: 10.1023/a:1023381027062.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. Semin Immunopathol. 2019;41(3):283–297. doi: 10.1007/s00281-019-00733-8.
   Google Scholar
• Beurel E, Lowell JA. Th17 cells in depression. Brain Behav Immun. 2018;69:28–34. doi: 10.1016/j.bbi.2017.08.001.
   Google Scholar
• Moser T, Akgün K, Proschmann U, et al. The role of TH17 cells in multiple sclerosis: therapeutic implications. Autoimmun Rev. 2020;19(10):102647. doi: 10.1016/j.autrev.2020.102647.
   Google Scholar
• Lucca LE, Dominguez-Villar M. Modulation of regulatory T cell function and stability by co-inhibitory receptors. Nat Rev Immunol. 2020;20(11):680–693. doi: 10.1038/s41577-020-0296-3.
   Google Scholar
• Eyerich K, Eyerich S. Th22 cells in allergic disease. Allergo J Int. 2015;24(1):1–7. doi: 10.1007/s40629-015-0039-3.
   Google Scholar
• Crotty S. Follicular helper CD4 T cells (T FH). Annu Rev Immunol. 2011;29(1):621–663. doi: 10.1146/annurev-immunol-031210-101400.
   PubMed Web of Science ®Google Scholar
• Ueno H. Human circulating T follicular helper cell subsets in health and disease. J clin Immunol. 2016;36(1):34–39. doi: 10.1007/s10875-016-0268-3.
   Google Scholar
• Weyand CM, Goronzy JJ. Immunometabolism in early and late stages of rheumatoid arthritis. Nat Rev Rheumatol. 2017;13(5):291–301. doi: 10.1038/nrrheum.2017.49.
   Google Scholar
• Ferreira LMR, Muller YD, Bluestone JA, et al. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019;18(10):749–769. doi: 10.1038/s41573-019-0041-4.
   Google Scholar
• Chao CC, Chen SJ, Adamopoulos IE, et al. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity. 2011;44(3):243–252. doi: 10.3109/08916934.2010.517815.
   PubMed Web of Science ®Google Scholar
• Scally SW, Petersen J, Law SC, et al. A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med. 2013;210(12):2569–2582. doi: 10.1084/jem.20131241.
   PubMed Web of Science ®Google Scholar
• Fox DA. The role of T cells in the immunopathogenesis of rheumatoid arthritis. Arthritis Rheum. 1997;40(4):598–609. doi: 10.1002/art.1780400403.
   PubMed Web of Science ®Google Scholar
• Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6(11):1133–1141. doi: 10.1038/ni1261.
   PubMed Web of Science ®Google Scholar
• Lubberts E, Koenders M, van den Berg WB. The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther. 2005;7(1):29–37. doi: 10.1186/ar1478.
   PubMed Web of Science ®Google Scholar
• Benedetti G, Miossec P. Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol. 2014;44(2):339–347. doi: 10.1002/eji.201344184.
   PubMed Web of Science ®Google Scholar
• Han L, Yang J, Wang X, et al. Th17 cells in autoimmune diseases. Front Med. 2015;9(1):10–19. doi: 10.1007/s11684-015-0388-9.
   Google Scholar
• Hirota K, Hashimoto M, Yoshitomi H, et al. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med. 2007;204(1):41–47. doi: 10.1084/jem.20062259.
   PubMed Web of Science ®Google Scholar
• Church LD, Filer AD, Hidalgo E, et al. Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression. Arthritis Res Ther. 2010;12(5):R184. doi: 10.1186/ar3152.
   PubMed Web of Science ®Google Scholar
• van Hamburg JP, Asmawidjaja PS, Davelaar N, et al. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 2011;63(1):73–83. doi: 10.1002/art.30093.
   PubMed Web of Science ®Google Scholar
• Komatsu N, Okamoto K, Sawa S, et al. Pathogenic conversion of Foxp3 + T cells into TH17 cells in autoimmune arthritis. Nat Med. 2014;20(1):62–68. doi: 10.1038/nm.3432.
   PubMed Web of Science ®Google Scholar
• Jiang Q, Yang G, Liu Q, et al. Function and role of regulatory T cells in rheumatoid arthritis. Front Immunol. 2021;12:626193. doi: 10.3389/fimmu.2021.626193.
   Google Scholar
• Li S, Yin H, Zhang K, et al. Effector T helper cell populations are elevated in the bone marrow of rheumatoid arthritis patients and correlate with disease severity. Sci Rep. 2017;7(1):4776. doi: 10.1038/s41598-017-05014-8.
   PubMedGoogle Scholar
• Cao D, van Vollenhoven R, Klareskog L, et al. Open access CD25 bright CD4 + regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res Ther. 2004;6(4):335–346. doi: 10.1186/ar1192.
   PubMed Web of Science ®Google Scholar
• Yu M, Cavero V, Lu Q, et al. Follicular helper T cells in rheumatoid arthritis. Clin Rheumatol. 2015;34(9):1489–1493. doi: 10.1007/s10067-015-3028-5.
   PubMed Web of Science ®Google Scholar
• Chakera A, Bennett SC, Morteau O, et al. The phenotype of circulating follicular-helper T cells in patients with rheumatoid arthritis defines CD200 as a potential therapeutic target. Clin Dev Immunol. 2012;2012:948218–948210. doi: 10.1155/2012/948218.
   PubMedGoogle Scholar
• Arroyo-Villa I, Bautista-Caro MB, Balsa A, et al. Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity. PLOS One. 2012;7(8):e42189. doi: 10.1371/journal.pone.0042189.
   PubMed Web of Science ®Google Scholar
• Liao J, Liang G, Xie S, et al. CD40L demethylation in CD4+ T cells from women with rheumatoid arthritis. Clin Immunol. 2012;145(1):13–18. doi: 10.1016/j.clim.2012.07.006.
   PubMed Web of Science ®Google Scholar
• Dai S, Jia R, Zhang X, et al. The PD-1/PD-Ls pathway and autoimmune diseases. Cell immunol. 2014;290(1):72–79. doi: 10.1016/j.cellimm.2014.05.006.
   Google Scholar
• Raptopoulou AP, Bertsias G, Makrygiannakis D, et al. The programmed death 1/programmed death ligand 1 inhibitory pathway is up-regulated in rheumatoid synovium and regulates peripheral T cell responses in human and murine arthritis. Arthritis Rheum. 2010;62(7):1870–1880. doi: 10.1002/art.27500.
   PubMedGoogle Scholar
• Weyand CM, Goronzy JJ. Immunometabolism in the development of rheumatoid arthritis. Immunol Rev. 2020;284(1):177–187. doi: 10.1111/imr.12838.
   Google Scholar
• Chimenti MS, Triggianese P, Conigliaro P, et al. The interplay between inflammation and metabolism in rheumatoid arthritis. Cell Death Dis. 2015;6(9):e1887. doi: 10.1038/cddis.2015.246.
   Google Scholar
• Petrasca A, Phelan JJ, Ansboro S, et al. Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in rheumatoid arthritis. Rheumatology. 2020;59(10):2816–2828. doi: 10.1093/rheumatology/kez682.
   PubMed Web of Science ®Google Scholar
• Li Y, Goronzy JJ, Weyand CM. DNA damage, metabolism and aging in pro-inflammatory T cells: rheumatoid arthritis as a model system. Exp Gerontol. 2018;105:118–127. doi: 10.1016/j.exger.2017.10.027.
   Google Scholar
• Balyan R, Gautam N, Gascoigne NRJ. The ups and downs of metabolism during the lifespan of a t cell. Int J Mol Sci. 2020;21:1–22.
   Google Scholar
• Maciolek JA, Alex Pasternak J, Wilson HL. Metabolism of activated T lymphocytes. Curr Opin Immunol. 2014;27:60–74. doi: 10.1016/j.coi.2014.01.006.
   PubMed Web of Science ®Google Scholar
• Hu Z, Zou Q, Su B. Regulation of T cell immunity by cellular metabolism. Front Med. 2018;12:463–472. doi: 10.1007/s11684-018-0668-2.
   Google Scholar
• Kolan SS, Li G, Wik JA, et al. Cellular metabolism dictates T cell effector function in health and disease. Scand J Immunol. 2020;92(5):e12956. doi: 10.1111/sji.12956.
   Google Scholar
• Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27(1):591–619. doi: 10.1146/annurev.immunol.021908.132706.
   PubMed Web of Science ®Google Scholar
• Bishop EL, Gudgeon N, Dimeloe S. Control of T cell metabolism by cytokines and hormones. Front Immunol. 2021;12:653605. doi: 10.3389/fimmu.2021.653605.
   Google Scholar
• Spolski R, Gromer D, Leonard WJ. The γc family of cytokines: fine-tuning signals from IL-2 and IL-21 in the regulation of the immune response. F1000Res. 2017;6:1872. doi: 10.12688/f1000research.12202.1.
   Google Scholar
• Chehtane M, Khaled AR. Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene. Am J Physiol Cell Physiol. 2010;298(6):C1560–C1571. doi: 10.1152/ajpcell.00506.2009.
   PubMed Web of Science ®Google Scholar
• Richer MJ, Pewe LL, Hancox LS, et al. Inflammatory IL-15 is required for optimal memory T cell responses. J Clin Invest. 2015;125(9):3477–3490. doi: 10.1172/JCI81261.
   PubMed Web of Science ®Google Scholar
• Kato H, Perl A. Blockade of treg cell differentiation and function by the interleukin-21–mechanistic target of rapamycin axis via suppression of autophagy in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2018;70(3):427–438. doi: 10.1002/art.40380.
   PubMed Web of Science ®Google Scholar
• Buck MD, O’Sullivan D, Klein Geltink RI, et al. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 2016;166(1):63–76. doi: 10.1016/j.cell.2016.05.035.
   PubMed Web of Science ®Google Scholar
• Ron-Harel N, Santos D, Ghergurovich JM, et al. Mitochondrial biogenesis and proteome remodeling promote one-Carbon metabolism for T cell activation. Cell Metab. 2016;24(1):104–117. doi: 10.1016/j.cmet.2016.06.007.
   PubMed Web of Science ®Google Scholar
• Franchina DG, Dostert C, Brenner D. Reactive oxygen species: involvement in T cell signaling and metabolism. Trends Immunol. 2018;39(6):489–502. doi: 10.1016/j.it.2018.01.005.
   Google Scholar
• Almeida L, Lochner M, Berod L, et al. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016;28(5):514–524. doi: 10.1016/j.smim.2016.10.009.
   Google Scholar
• Soto-Heredero G, Gómez de las Heras MM, Gabandé-Rodríguez E, et al. Glycolysis – a key player in the inflammatory response. FEBS J. 2020;24(1):3350–3369. doi: 10.1111/febs.15327.
   Google Scholar
• Liberti M v, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41(3):211–218. doi: 10.1016/j.tibs.2015.12.001.
   Google Scholar
• Peng M, Yin N, Chhangawala S, et al. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016;354(6311):481–484. doi: 10.1126/science.aaf6284.
   PubMed Web of Science ®Google Scholar
• Wahl DR, Byersdorfer CA, Ferrara JLM, et al. Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol Rev. 2012;249(1):104–115.
   PubMedGoogle Scholar
• Schwenk RW, Holloway GP, Luiken JJFP, et al. Fatty acid transport across the cell membrane: regulation by fatty acid transporters. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):149–154. doi: 10.1016/j.plefa.2010.02.029.
   PubMed Web of Science ®Google Scholar
• Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4 + T cell subsets. J Immunol. 2011;186(6):3299–3303. doi: 10.4049/jimmunol.1003613.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ertl HCJ. Starved and asphyxiated: how can CD8+ T cells within a tumor microenvironment prevent tumor progression. Front Immunol. 2016;7:32. doi: 10.3389/fimmu.2016.00032.
   PubMed Web of Science ®Google Scholar
• Fraser KA, Schenkel JM, Jameson SC, et al. Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. Immunity. 2013;39(1):171–183. doi: 10.1016/j.immuni.2013.07.003.
   PubMed Web of Science ®Google Scholar
• Brown EJ, Albers MW, Shin TB, et al. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature. 1994;369(6483):756–758. doi: 10.1038/369756a0.
   Google Scholar
• Delgoffe GM, Kole TP, Zheng Y, et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity. 2009;30(6):832–844. doi: 10.1016/j.immuni.2009.04.014.
   PubMed Web of Science ®Google Scholar
• Kurebayashi Y, Nagai S, Ikejiri A, et al. PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORγ. Cell Rep. 2012;1(4):360–373. doi: 10.1016/j.celrep.2012.02.007.
   PubMed Web of Science ®Google Scholar
• Lee K, Gudapati P, Dragovic S, et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010;32(6):743–753. doi: 10.1016/j.immuni.2010.06.002.
   PubMed Web of Science ®Google Scholar
• Wang R, Dillon CP, Shi LZ, et al. The transcription factor myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 2011;35(6):871–882. doi: 10.1016/j.immuni.2011.09.021.
   PubMed Web of Science ®Google Scholar
• Hardie DG, Scott JW, Pan DA, et al. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett. 2003;546(1):113–120. doi: 10.1016/s0014-5793(03)00560-x.
   Google Scholar
• Tamás P, Hawley SA, Clarke RG, et al. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes. J Exp Med. 2006;203(7):1665–1670. doi: 10.1084/jem.20052469.
   PubMed Web of Science ®Google Scholar
• Maciver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31(1):259–283. doi: 10.1146/annurev-immunol-032712-095956.
   PubMed Web of Science ®Google Scholar
• Zhao Z, Condomines M, van der Stegen SJC, et al. Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell. 2015;28(4):415–428. doi: 10.1016/j.ccell.2015.09.004.
   PubMed Web of Science ®Google Scholar
• Phan AT, Goldrath AW, Glass CK. Metabolic and epigenetic coordination of T cell and macrophage immunity. Immunity. 2017;46(5):714–729. doi: 10.1016/j.immuni.2017.04.016.
   Google Scholar
• Sachpekidis C, Larribère L, Kopp-Schneider A, et al. Can benign lymphoid tissue changes in 18F-FDG PET/CT predict response to immunotherapy in metastatic melanoma? Cancer Immunol Immunother. 2022;68(2):297–303. doi: 10.1007/s00262-018-2279-9.
   Google Scholar
• Ivashko IN, Kolesar JM. Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. Am J Health Syst Pharm. 2016;73(4):193–201. doi: 10.2146/ajhp140768.
   PubMed Web of Science ®Google Scholar
• Vella S, Conti M, Tasso R, et al. Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells. Int J Cancer. 2012;130(7):1484–1493. doi: 10.1002/ijc.26173.
   PubMed Web of Science ®Google Scholar
• Eleftheriadis T, Pissas G, Karioti A, et al. Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory T-cell differentiation in alloreactive human lymphocytes. J Basic Clin Physiol Pharmacol. 2013;24(4):271–276. doi: 10.1515/jbcpp-2013-0001.
   PubMedGoogle Scholar
• Viollet B, Guigas B, Sanz Garcia N, et al. Cellular and molecular mechanisms of metformin: an overview. Clin Sci. 2012;122(6):253–270. doi: 10.1042/CS20110386.
   PubMed Web of Science ®Google Scholar
• Dandapani M, Hardie DG. AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? Biochem Soc Trans. 2013;41(2):687–693. doi: 10.1042/BST20120351.
   PubMedGoogle Scholar
• Lee SY, Lee SH, Yang EJ, et al. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/treg balance. PLOS One. 2015;10(9):e0135858. doi: 10.1371/journal.pone.0135858.
   PubMed Web of Science ®Google Scholar
• Granchi C, Paterni I, Rani R, et al. Small-molecule inhibitors of human LDH5. Future Med Chem. 2013;5(16):1967–1991. doi: 10.4155/fmc.13.151.
   PubMed Web of Science ®Google Scholar
• Huber V, Camisaschi C, Berzi A, et al. Cancer acidity: an ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol. 2017;43:74–89. doi: 10.1016/j.semcancer.2017.03.001.
   PubMed Web of Science ®Google Scholar
• Kouidhi S, Ben AF, Elgaaied AB. Targeting tumor metabolism: a new challenge to improve immunotherapy. Front Immunol. 2018;9:353. doi: 10.3389/fimmu.2018.00353.
   PubMed Web of Science ®Google Scholar
• van der Mijn JC, Panka DJ, Geissler AK, et al. Novel drugs that target the metabolic reprogramming in renal cell cancer. Cancer Metab. 2016;4(1):14. doi: 10.1186/s40170-016-0154-8.
   PubMedGoogle Scholar
• Pollizzi KN, Powell JD. Integrating canonical and metabolic signalling programmes in the regulation of T cell responses. Nat Rev Immunol. 2014;14(7):435–446. doi: 10.1038/nri3701.
   Google Scholar
• Cao Y, Rathmell JC, Macintyre AN. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells. PLOS One. 2014;9(8):e104104. doi: 10.1371/journal.pone.0104104.
   PubMed Web of Science ®Google Scholar
• Zeng H, Cohen S, Guy C, et al. mTORC1 and mTORC2 kinase signaling and glucose metabolism drive follicular helper T cell differentiation. Immunity. 2016;45(3):540–554. doi: 10.1016/j.immuni.2016.08.017.
   PubMed Web of Science ®Google Scholar
• Macintyre AN, Gerriets VA, Nichols AG, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014;20(1):61–72. doi: 10.1016/j.cmet.2014.05.004.
   PubMed Web of Science ®Google Scholar
• Yecies JL, Manning BD. Transcriptional control of cellular meta­bolism by mtor signaling. Cancer Res. 2011;71(8):2815–2820. doi: 10.1158/0008-5472.CAN-10-4158.
   PubMed Web of Science ®Google Scholar
• Sener Z, Cederkvist FH, Volchenkov R, et al. T helper cell activation and expansion is sensitive to glutaminase inhibition under both hypoxic and normoxic conditions. PLoS One. 2016;11(7):e0160291. doi: 10.1371/journal.pone.0160291.
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Laurence A, Yang XP, et al. Generation of pathogenic TH 17 cells in the absence of TGF-β 2 signalling. Nature. 2010;467(7318):967–971. doi: 10.1038/nature09447.
   PubMed Web of Science ®Google Scholar
• Jain R, Chen Y, Kanno Y, et al. Interleukin-23-induced transcription factor blimp-1 promotes pathogenicity of T helper 17 cells. Immunity. 2016;44(1):131–142. doi: 10.1016/j.immuni.2015.11.009.
   PubMed Web of Science ®Google Scholar
• Heink S, Yogev N, Garbers C, et al. Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T H 17 cells. Nat Immunol. 2017;18(1):74–85. doi: 10.1038/ni.3632.
   PubMed Web of Science ®Google Scholar
• Cui G, Staron MM, Gray SM, et al. IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell. 2015;161(4):750–761. doi: 10.1016/j.cell.2015.03.021.
   PubMed Web of Science ®Google Scholar
• Geiger R, Rieckmann JC, Wolf T, et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell. 2016;167(3):829–842.e13. doi: 10.1016/j.cell.2016.09.031.
   PubMed Web of Science ®Google Scholar
• Phan AT, Doedens AL, Palazon A, et al. Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection. Immunity. 2016;45(5):1024–1037. doi: 10.1016/j.immuni.2016.10.017.
   PubMed Web of Science ®Google Scholar
• Pollizzi KN, Patel CH, Sun IH, et al. mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. J Clin Invest. 2015;125(5):2090–2108. doi: 10.1172/JCI77746.
   PubMed Web of Science ®Google Scholar
• Ma EH, Bantug G, Griss T, et al. Serine is an essential metabolite for effector T cell expansion. Cell Metab. 2017;25(2):345–357. doi: 10.1016/j.cmet.2016.12.011.
   PubMed Web of Science ®Google Scholar
• Li W, Qu G, Choi SC, et al. Targeting T cell activation and lupus autoimmune phenotypes by inhibiting glucose transporters. Front Immunol. 2019;10:833. doi: 10.3389/fimmu.2019.00833.
   PubMed Web of Science ®Google Scholar
• Wen Z, Jin K, Shen Y, et al. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation. Nat Immunol. 2019;20(3):313–325. doi: 10.1038/s41590-018-0296-7.
   PubMed Web of Science ®Google Scholar
• Verbist KC, Guy CS, Milasta S, et al. Metabolic maintenance of cell asymmetry following division in activated T lymphocytes. Nature. 2016;532(7599):389–393. doi: 10.1038/nature17442.
   PubMed Web of Science ®Google Scholar
• Yang JZ, Zhang JQ, Sun LX. Mechanisms for T cell tolerance induced with granulocyte colony-stimulating factor. Mol Immunol. 2016;70:56–62. doi: 10.1016/j.molimm.2015.12.006.
   PubMed Web of Science ®Google Scholar