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Artesunate targets cellular metabolism to regulate the Th17/Treg cell balance

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Abstract

Introduction

Metabolic reprogramming is one of the important mechanisms of cell differentiation, and different cells have different preferences for energy sources. During the differentiation of naive CD4 + T cells into Th17 and Treg cells, these cells show specific energy metabolism characteristics. Th17 cells depend on enhanced glycolysis, fatty acid synthesis, and glutaminolysis. In contrast, Treg cells are dependent on oxidative phosphorylation, fatty acid oxidation, and amino acid depletion. As a potent antimalarial drug, artesunate has been shown to modulate the Th17/Treg imbalance and regulate cell metabolism.

Methodology

Relevant literatures on ART, cellular metabolism, glycolysis, lipid metabolism, amino acid metabolism, CD4 + T cells, Th17 cells, and Treg cells published from January 1, 2010 to now were searched in PubMed database.

Conclusion

In this review, we will highlight recent advances in which artesunate can restore the Th17/Treg imbalance in disease states by altering T-cell metabolism to influence differentiation and lineage selection. Data from the current study show that few studies have focused on the effect of ART on cellular metabolism. ART can affect the metabolic characteristics of T cells (glycolysis, lipid metabolism, and amino acid metabolism) and interfere with their differentiation lineage, thereby regulating the balance of Th17/Treg and alleviating the symptoms of the disease.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

ABCA1:

ATP-binding cassette transporter A1

ABCG1:

ATP-binding cassette transporter G1

ACC:

Acetyl-CoA carboxylase

AMPK:

AMP-activated protein kinase

APC:

Antigen-presenting cells

ART:

Artesunate

AST:

Aspartate aminotransferase

c-Rel:

REL proto-oncogene

c-Myc:

MYC proto-oncogene

CCND1:

Cyclin D1

CEBPα:

CCAAT/enhancer binding protein α

ERK:

Extracellular regulated protein kinases

FAO:

Fatty acid β-oxidation

FAS:

Fatty acid synthesis

FASN:

Fatty acid synthase

Fas:

Fas cell surface death receptor

Foxp3:

Forkhead Box p3

GLS:

Glutaminase

GLUD:

Glutamate dehydrogenase

Glut1:

Glucose transporter-1

GOT:

Aspartate aminotransferase

GSH:

Glutathione

GST:

Glutathione S-transferase

G-6-P:

Glucose 6-phosphate

HDAC3:

Histone deacetylase 3

HIF1-α:

Hypoxia-inducible factor-1α

Hk2:

Hexokinase 2

HMGCR:

3-Hydroxy-3-methylglutaryl-CoA reductase

ICER:

Inducible cAMP Early Repressor

IFNγ:

Interferon gamma

IL-17:

Interleukin 17

IL-23R:

Interleukin 23 receptor

IRF4:

Interferon regulatory factor 4

iTreg:

Induced T cells

JAK-STAT:

Janus kinase/signal transducer and activator of transcription

LDHA:

Lactate dehydrogenase A

LDLR:

Low-density lipoprotein receptor

LKB1:

Liver kinase B1

LXRs:

Liver X receptors

MAPK:

Mitogen-activated protein kinase

mTORC1/2:

Mammalian target of rapamycin complex 1/2

nTreg:

Natural regulatory T cells

PHD3:

Prolyl hydroxylase 3

PI3K/Akt:

Phosphatidylinositol 3-kinase/protein kinase B

PKM2:

Pyruvate kinase isoform 2

PPARs:

Peroxisome proliferator-activated receptors

PPARγ:

Peroxisome proliferator-activated receptor gamma

PRMTs:

Protein arginine methyltransferases

PTXF:

Pentoxifylline

Ras:

Rat sarcoma

RORC2:

Retinoic acid receptor-associated orphan receptor 2

ROS:

Reactive oxygen species

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

SLC1A5:

Solute carrier family 1 member 5

SLC2A1:

Solute carrier family 2 member 1

SR-BI:

Scavenger receptor class B type I

SREBPs:

Sterol response element-binding proteins

S6K1:

Ribosomal protein S6 kinase B1

TET1/2:

Tet methylcytosine dioxygenase 1/2

Tfh:

T follicular helper cells

Th17:

T helper type cells

Treg:

Regulatory T cells

Tr1:

Tregulatory1

α-ΚG:

Alpha-ketoglutaric acid

2-DG:

2-Deoxyglucose

2-HG:

2-Hydroxyglutaric acid

3-BP:

3-Bromopyruvate

References

  1. Faas M, Ipseiz N, Ackermann J, Culemann S, Grüneboom A, Schröder F, et al. IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation. Immunity. 2021;54:2531-2546.e5.

    Article  CAS  PubMed  Google Scholar 

  2. Wang H, Yang Y, Liu J, Qian L. Direct cell reprogramming: approaches, mechanisms and progress. Nat Rev Mol Cell Biol. 2021;22:410–24.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zhang Y, Li F, Chen C, Li Y, Xie W, Huang D, et al. RAGE-mediated T cell metabolic reprogramming shapes T cell inflammatory response after stroke. J Cereb Blood Flow Metab. 2022;42:952–65.

    Article  CAS  PubMed  Google Scholar 

  4. Deng J, Lu C, Zhao Q, Chen K, Ma S, Li Z. The Th17/Treg cell balance: crosstalk among the immune system, bone and microbes in periodontitis. J Periodontal Res. 2022;57:246–55.

    Article  CAS  PubMed  Google Scholar 

  5. Yuan M, Qian X, Huang Y, Ma X, Duan F, Yang Y, et al. Th17 Activation and Th17/Treg imbalance in prolonged anterior intraocular inflammation after ocular alkali burn. Int J Mol Sci. 2022;23:7075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wang C, Zhou W, Su G, Hu J, Yang P. Progranulin suppressed autoimmune uveitis and autoimmune neuroinflammation by inhibiting Th1/Th17 cells and promoting Treg cells and M2 macrophages. Neurol Neuroimmunol Neuroinflamm. 2022;9: e1133.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Muik A, Adams HC, Gieseke F, Altintas I, Schoedel KB, Blum JM, et al. DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4–1BB agonist activity. J Immunother Cancer. 2022;10: e004322.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Shenoy AT, De Lyon AC, Arafa EI, Salwig I, Barker KA, Korkmaz FT, et al. Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity. Nat Commun. 2021;12:5834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Balyan R, Gautam N, Gascoigne NRJ. The ups and downs of metabolism during the lifespan of a T cell. Int J Mol Sci. 2020;21:7972.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Almeida L, Dhillon-LaBrooy A, Carriche G, Berod L, Sparwasser T. CD4+ T-cell differentiation and function: unifying glycolysis, fatty acid oxidation, polyamines NAD mitochondria. J Allergy Clin Immunol. 2021;148:16–32.

    Article  CAS  PubMed  Google Scholar 

  11. Miao Y, Zhang C, Yang L, Zeng X, Hu Y, Xue X, et al. The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. Cell Commun Signal. 2022;20:48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cai F, Jin S, Chen G. The effect of lipid metabolism on CD4+ T cells. Mediators Inflamm. 2021;2021:1–8.

    Article  Google Scholar 

  13. Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R, Ma EH, et al. Etomoxir actions on regulatory and memory T cells are independent of Cpt1a-mediated fatty acid oxidation. Cell Metab. 2018;28:504-515.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu S, Liu Z, Shan Z, Liu Y, Chen T, Fang L, et al. Skewed Th17/Treg balance during progression and malignant transformation of oral submucous fibrosis. Oral Dis. 2022;28:2119–30.

    Article  PubMed  Google Scholar 

  15. Ma Y, Liu C, Xi G, Guan Y, Tang Y, Zhang J, et al. Bioinformatic analysis and cellular assays identify substance P influencing Th17/Treg differentiation via the MyD88 pathway as a potential contributor to the progression of asthma and allergic rhinitis. Dis Markers. 2022;2022:1–11.

    Google Scholar 

  16. Huang F, Wong P, Li J, Lv Z, Xu L, Zhu G, et al. Osteoimmunology: The correlation between osteoclasts and the Th17/Treg balance in osteoporosis. J Cell Mol Med. 2022;26:3591–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang S, Gang X, Yang S, Cui M, Sun L, Li Z, et al. The alterations in and the role of the Th17/Treg balance in metabolic diseases. Front Immunol. 2021. https://doi.org/10.3389/fimmu.2021.678355.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ma N, Zhang Z, Liao F, Jiang T, Tu Y. The birth of artemisinin. Pharmacol Ther. 2020;216: 107658.

    Article  CAS  PubMed  Google Scholar 

  19. Feng X, Cao S, Qiu F, Zhang B. Traditional application and modern pharmacological research of Artemisia annua L. Pharmacol Ther. 2020;216: 107650.

    Article  CAS  PubMed  Google Scholar 

  20. Tu Y. Artemisinin-A gift from traditional Chinese medicine to the world (nobel lecture). Angew Chem Int Ed. 2016;55:10210–26.

    Article  CAS  Google Scholar 

  21. Efferth T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017;46:65–83.

    Article  CAS  PubMed  Google Scholar 

  22. Efferth T, Oesch F. The immunosuppressive activity of artemisinin-type drugs towards inflammatory and autoimmune diseases. Med Res Rev. 2021;41:3023–61.

    Article  CAS  PubMed  Google Scholar 

  23. Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacol Res. 2020;158: 104901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bai X-Y, Liu P, Chai Y-W, Wang Y, Ren S-H, Li Y-Y, et al. Artesunate attenuates 2, 4-dinitrochlorobenzene-induced atopic dermatitis by down-regulating Th17 cell responses in BALB/c mice. Eur J Pharmacol. 2020;874: 173020.

    Article  CAS  PubMed  Google Scholar 

  25. Liu J, Hong X, Lin D, Luo X, Zhu M, Mo H. Artesunate influences Th17/Treg lymphocyte balance by modulating Treg apoptosis and Th17 proliferation in a murine model of rheumatoid arthritis. Exp Ther Med. 2017;13:2267–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xiao F, Rui K, Han M, Zou L, Huang E, Tian J, et al. Artesunate suppresses Th17 response via inhibiting IRF4-mediated glycolysis and ameliorates Sjog̈ren’s syndrome. Signal Transduct Target Ther. 2022;7:274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ruterbusch M, Pruner KB, Shehata L, Pepper M. In vivo CD4 + T cell differentiation and function: revisiting the Th1/Th2 paradigm. Annu Rev Immunol. 2020;38:705–25.

    Article  CAS  PubMed  Google Scholar 

  29. Maggi L, Santarlasci V, Capone M, Peired A, Frosali F, Crome SQ, et al. CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC. Eur J Immunol. 2010;40:2174–81.

    Article  CAS  PubMed  Google Scholar 

  30. Crome SQ, Wang AY, Kang CY, Levings MK. The role of retinoic acid‐related orphan receptor variant 2 and IL‐17 in the development and function of human CD4 &plus. T cells Eur J Immunol. 2009;39:1480–93.

    Article  CAS  PubMed  Google Scholar 

  31. Mazzoni A, Santarlasci V, Maggi L, Capone M, Rossi MC, Querci V, et al. Demethylation of the RORC2 and IL17A in human CD4+ T lymphocytes defines Th17 origin of nonclassic Th1 cells. J Immunol. 2015;194:3116–26.

    Article  CAS  PubMed  Google Scholar 

  32. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.

    Article  CAS  PubMed  Google Scholar 

  33. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.

    Article  CAS  PubMed  Google Scholar 

  34. Loos J, Schmaul S, Noll TM, Paterka M, Schillner M, Löffel JT, et al. Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy. J Neuroinflammation. 2020;17:357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Millier MJ, Fanning NC, Frampton C, Stamp LK, Hessian PA. Plasma interleukin-23 and circulating IL-17A+IFNγ+ ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis. Arthritis Res Ther. 2022;24:57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jiang C, Wang H, Xue M, Lin L, Wang J, Cai G, et al. Reprograming of peripheral Foxp3+ regulatory T cell towards Th17-like cell in patients with active systemic lupus erythematosus. Clin Immunol. 2019;209: 108267.

    Article  CAS  PubMed  Google Scholar 

  37. Shen X, Zhang H, Xie H, Chen L, Li S, Zheng J, et al. Reduced CCR6+IL-17A+Treg cells in blood and CCR6-dependent accumulation of IL-17A+Treg cells in lungs of patients with allergic asthma. Front Immunol. 2021. https://doi.org/10.3389/fimmu.2021.710750.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–64.

    Article  CAS  PubMed  Google Scholar 

  39. Schuster M, Plaza-Sirvent C, Visekruna A, Huehn J, Schmitz I. Generation of Foxp3+CD25− regulatory T-cell precursors requires c-Rel and IκBNS. Front Immunol. 2019. https://doi.org/10.3389/fimmu.2019.01583.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ohkura N, Sakaguchi S. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30:465–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhou W-J, Yang H-L, Shao J, Mei J, Chang K-K, Zhu R, et al. Anti-inflammatory cytokines in endometriosis. Cell Mol Life Sci. 2019;76:2111–32.

    Article  CAS  PubMed  Google Scholar 

  42. Laurence A, Amarnath S, Mariotti J, Kim YC, Foley J, Eckhaus M, et al. STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease. Immunity. 2012;37:209–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dong Y, Yang C, Pan F. Post-translational regulations of Foxp3 in Treg cells and their therapeutic applications. Front Immunol. 2021. https://doi.org/10.3389/fimmu.2021.626172.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Barbi J, Pardoll D, Pan F. Treg functional stability and its responsiveness to the microenvironment. Immunol Rev. 2014;259:115–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Muñoz-Rojas AR, Mathis D. Tissue regulatory T cells: regulatory chameleons. Nat Rev Immunol. 2021;21:597–611.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486:549–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Song X, Sun X, Oh SF, Wu M, Zhang Y, Zheng W, et al. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature. 2020;577:410–5.

    Article  CAS  PubMed  Google Scholar 

  48. Yan Y, Ramanan D, Rozenberg M, McGovern K, Rastelli D, Vijaykumar B, et al. Interleukin-6 produced by enteric neurons regulates the number and phenotype of microbe-responsive regulatory T cells in the gut. Immunity. 2021;54:499-513.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cottrez F, Groux H. Specialization in tolerance: innate CD4+CD25+ versus acquired TR1 and TH3 regulatory T cells. 1. Transplantation. 2004;77:S12–5.

    Article  PubMed  Google Scholar 

  50. Vences-Catalán F, Rajapaksa R, Srivastava MK, Marabelle A, Kuo C-C, Levy R, et al. Tetraspanin CD81 promotes tumor growth and metastasis by modulating the functions of T regulatory and myeloid-derived suppressor cells. Cancer Res. 2015;75:4517–26.

    Article  PubMed  Google Scholar 

  51. Cook L, Stahl M, Han X, Nazli A, MacDonald KN, Wong MQ, et al. Suppressive and gut-reparative functions of human type 1 T regulatory cells. Gastroenterology. 2019;157:1584–98.

    Article  CAS  PubMed  Google Scholar 

  52. Ryall JG, Cliff T, Dalton S, Sartorelli V. Metabolic reprogramming of stem cell epigenetics. Cell Stem Cell. 2015;17:651–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Almeida L, Lochner M, Berod L, Sparwasser T. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016;28:514–24.

    Article  CAS  PubMed  Google Scholar 

  54. Lunt SY, van der Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27:441–64.

    Article  CAS  PubMed  Google Scholar 

  55. Fernie AR, Carrari F, Sweetlove LJ. Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol. 2004;7:254–61.

    Article  CAS  PubMed  Google Scholar 

  56. Peek CB, Levine DC, Cedernaes J, Taguchi A, Kobayashi Y, Tsai SJ, et al. Circadian clock interaction with HIF1α mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle. Cell Metab. 2017;25:86–92.

    Article  CAS  PubMed  Google Scholar 

  57. Nicoli F, Paul S, Appay V. Harnessing the induction of CD8+ T-cell responses through metabolic regulation by pathogen-recognition-receptor triggering in antigen presenting cells. Front Immunol. 2018;9:2372.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Chopp LB, Gopalan V, Ciucci T, Ruchinskas A, Rae Z, Lagarde M, et al. An integrated epigenomic and transcriptomic map of mouse and human αβ T Cell development. Immunity. 2020;53:1182-1201.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Martínez-Méndez D, Mendoza L, Villarreal C, Huerta L. Continuous modeling of T CD4 lymphocyte activation and function. Front Immunol. 2021;12:4424.

    Article  Google Scholar 

  60. Cluxton D, Petrasca A, Moran B, Fletcher JM. Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis. Front Immunol. 2019;10:115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Daneshmandi S, Cassel T, Higashi RM, Fan TW-M, Seth P. Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function. Elife. 2021;10:e67476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sukonina V, Ma H, Zhang W, Bartesaghi S, Subhash S, Heglind M, et al. FOXK1 and FOXK2 regulate aerobic glycolysis. Nature. 2019;566:279–83.

    Article  CAS  PubMed  Google Scholar 

  63. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186:3299–303.

    Article  CAS  PubMed  Google Scholar 

  64. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149:274–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang H, Long L, Zhou P, Chapman NM, Chi H. mTOR signaling at the crossroads of environmental signals and T-cell fate decisions. Immunol Rev. 2020;295:15–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Szwed A, Kim E, Jacinto E. Regulation and metabolic functions of mTORC1 and mTORC2. Physiol Rev. 2021;101:1371–426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wu S, Zou M-H. AMPK, mitochondrial function, and cardiovascular disease. Int J Mol Sci. 2020;21:4987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yang Q, Liu X, Liu Q, Guan Z, Luo J, Cao G, et al. Roles of mTORC1 and mTORC2 in controlling γδ T1 and γδ T17 differentiation and function. Cell Death Differ. 2020;27:2248–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pandit M, Timilshina M, Chang J-H. LKB1-PTEN axis controls Th1 and Th17 cell differentiation via regulating mTORC1. J Mol Med. 2021;99:1139–50.

    Article  CAS  PubMed  Google Scholar 

  70. Siska PJ, van der Windt GJW, Kishton RJ, Cohen S, Eisner W, MacIver NJ, et al. Suppression of Glut1 and glucose metabolism by decreased Akt/mTORC1 signaling drives T cell impairment in B cell leukemia. J Immunol. 2016;197:2532–40.

    Article  CAS  PubMed  Google Scholar 

  71. Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693–733.

    Article  CAS  PubMed  Google Scholar 

  72. Gilmore TD, Kalaitzidis D, Liang M-C, Starczynowski DT. The c-Rel transcription factor and B-cell proliferation: a deal with the devil. Oncogene. 2004;23:2275–86.

    Article  CAS  PubMed  Google Scholar 

  73. Jeltsch KM, Hu D, Brenner S, Zöller J, Heinz GA, Nagel D, et al. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat Immunol. 2014;15:1079–89.

    Article  CAS  PubMed  Google Scholar 

  74. Okano T, Saegusa J, Nishimura K, Takahashi S, Sendo S, Ueda Y, et al. 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation. Sci Rep. 2017;7:42412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Fang Y, Shen Z-Y, Zhan Y-Z, Feng X-C, Chen K-L, Li Y-S, et al. CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis. Nat Commun. 2019;10:3981.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Jing Z, Liu Q, He X, Jia Z, Xu Z, Yang B, et al. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J Exp Clin Cancer Res. 2022;41:198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pacheco-Velázquez SC, Robledo-Cadena DX, Hernández-Reséndiz I, Gallardo-Pérez JC, Moreno-Sánchez R, Rodríguez-Enríquez S. Energy metabolism drugs block triple negative breast metastatic cancer cell phenotype. Mol Pharm. 2018;15:2151–64.

    Article  PubMed  Google Scholar 

  78. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, et al. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol. 2012;14:1295–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu M, Zhang Z, Wang H, Chen X, Jin C. Activation of AMPK by metformin promotes renal cancer cell proliferation under glucose deprivation through its interaction with PKM2. Int J Biol Sci. 2019;15:617–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Layman AAK, Deng G, O’Leary CE, Tadros S, Thomas RM, Dybas JM, et al. Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to prevent autoinflammatory disease. Nat Commun. 2017;8:15677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wei J, Long L, Yang K, Guy C, Shrestha S, Chen Z, et al. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nat Immunol. 2016;17:277–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 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;70:427–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. mTORC1 couples immune signals and metabolic programming to establish Treg-cell function. Nature. 2013;499:485–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Feng J, Dai W, Mao Y, Wu L, Li J, Chen K, et al. Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. J Exp Clin Cancer Res. 2020;39:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Maturu P, Jones D, Ruteshouser EC, Hu Q, Reynolds JM, Hicks J, et al. Role of cyclooxygenase-2 pathway in creating an immunosuppressive microenvironment and in initiation and progression of Wilms’ tumor. Neoplasia. 2017;19:237–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Patterson DG, Kania AK, Price MJ, Rose JR, Scharer CD, Boss JM. An IRF4–MYC–mTORC1 integrated pathway controls cell growth and the proliferative capacity of activated B cells during B cell differentiation in vivo. J Immunol. 2021;207:1798–811.

    Article  CAS  PubMed  Google Scholar 

  87. Mahnke J, Schumacher V, Ahrens S, Käding N, Feldhoff LM, Huber M, et al. Interferon regulatory factor 4 controls TH1 cell effector function and metabolism. Sci Rep. 2016;6:35521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bae S, Park PSU, Lee Y, Mun SH, Giannopoulou E, Fujii T, et al. MYC-mediated early glycolysis negatively regulates proinflammatory responses by controlling IRF4 in inflammatory macrophages. Cell Rep. 2021;35: 109264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Huang SC-C, Smith AM, Everts B, Colonna M, Pearce EL, Schilling JD, et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity. 2016;45:817–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang Y, Wang Y, Li Y, Huang C, Xiao X, Zhong Z, et al. Dihydroartemisinin and artesunate inhibit aerobic glycolysis via suppressing c-Myc signaling in non-small cell lung cancer. Biochem Pharmacol. 2022;198: 114941.

    Article  CAS  PubMed  Google Scholar 

  91. Jin J, Guo D, Wang Y, Jiao W, Li D, He Y. Artesunate inhibits the development of esophageal cancer by targeting HK1 to reduce glycolysis levels in areas with zinc deficiency. Front Oncol. 2022;12:1956.

    Google Scholar 

  92. Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K, et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014;20:1327–33.

    Article  CAS  PubMed  Google Scholar 

  93. Miao Y, Wu X, Xue X, Ma X, Yang L, Zeng X, et al. Morin, the PPARγ agonist, inhibits Th17 differentiation by limiting fatty acid synthesis in collagen-induced arthritis. Cell Biol Toxicol. 2022. https://doi.org/10.1007/s10565-022-09769-3.

    Article  PubMed  Google Scholar 

  94. Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci. 2020;117:31189–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Investig. 2002;109:1125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–40.

    Article  CAS  PubMed  Google Scholar 

  97. Brown MS, Goldstein JL. Sterol regulatory element binding proteins (SREBPs): controllers of lipid synthesis and cellular uptake. Nutr Rev. 2009;56:S1-3.

    Article  Google Scholar 

  98. Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 2010;39:171–83.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Ravacci GR, Brentani MM, Tortelli TC, Torrinhas RSMM, Santos JR, Logullo AF, et al. Docosahexaenoic acid modulates a HER2-associated lipogenic phenotype, induces apoptosis, and increases trastuzumab action in HER2-overexpressing breast carcinoma cells. Biomed Res Int. 2015;2015:1–13.

    Article  Google Scholar 

  100. Yuan M, Pino E, Wu L, Kacergis M, Soukas AA. Identification of Akt-independent regulation of hepatic lipogenesis by mammalian target of rapamycin (mTOR) complex 2. J Biol Chem. 2012;287:29579–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Guo Y, Zhao M, Bo T, Ma S, Yuan Z, Chen W, et al. Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol. Cell Res. 2019;29:151–66.

    Article  CAS  PubMed  Google Scholar 

  102. Mohamed A, Viveiros A, Williams K, de Posse CE. Aβ inhibits SREBP-2 activation through Akt inhibition. J Lipid Res. 2018;59:1–13.

    Article  CAS  PubMed  Google Scholar 

  103. Pallottini V, Guantario B, Martini C, Totta P, Filippi I, Carraro F, et al. Regulation of HMG-CoA reductase expression by hypoxia. J Cell Biochem. 2008;104:701–9.

    Article  CAS  PubMed  Google Scholar 

  104. Gualdoni GA, Mayer KA, Göschl L, Boucheron N, Ellmeier W, Zlabinger GJ. The AMP analog AICAR modulates the T reg /T h 17 axis through enhancement of fatty acid oxidation. FASEB J. 2016;30:3800–9.

    Article  CAS  PubMed  Google Scholar 

  105. Tao W, Cao W, Yu B, Chen H, Gong R, Luorong Q, et al. Hawk tea prevents high-fat diet-induced obesity in mice by activating the AMPK/ACC/SREBP1c signaling pathways and regulating the gut microbiota. Food Funct. 2022;13:6056–71.

    Article  CAS  PubMed  Google Scholar 

  106. Pang Y, Xu X, Xiang X, Li Y, Zhao Z, Li J, et al. High fat activates O-GlcNAcylation and affects AMPK/ACC pathway to regulate lipid metabolism. Nutrients. 2021;13:1740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Leung KL, Sanchita S, Pham CT, Davis BA, Okhovat M, Ding X, et al. Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellular programming. Clin Epigenetics. 2020;12:181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Liu D, Pang Q, Han Q, Shi Q, Zhang Q, Yu H. Wnt10b participates in regulating fatty acid synthesis in the muscle of zebrafish. Cells. 2019;8:1011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. He QJ, Wang P, Liu QQ, Wu QG, Li YF, Wang J, et al. Secreted Wnt6 mediates diabetes-associated centrosome amplification via its receptor FZD4. Am J Physiol Cell Physiol. 2020;318:C48-62.

    Article  CAS  PubMed  Google Scholar 

  110. Nishizuka M, Koyanagi A, Osada S, Imagawa M. Wnt4 and Wnt5a promote adipocyte differentiation. FEBS Lett. 2008;582:3201–5.

    Article  CAS  PubMed  Google Scholar 

  111. Yu W, Chen C-Z, Peng Y, Li Z, Gao Y, Liang S, et al. KRAS affects adipogenic differentiation by regulating autophagy and MAPK activation in 3T3-L1 and C2C12 cells. Int J Mol Sci. 2021;22:13630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Wang S, Sun L. Silencing Aurora-kinase-A (AURKA) reinforced the sensitivity of diffuse large B-cell lymphoma cells to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) via suppressing β-Catenin and RAS-extracellular signal-regulated protein kinase (ERK1/2) pathway. Bioengineered. 2021;12:8296–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Pan S, Zhang L, Liu Z, Xing H. Myostatin suppresses adipogenic differentiation and lipid accumulation by activating crosstalk between ERK1/2 and PKA signaling pathways in porcine subcutaneous preadipocytes. J Anim Sci. 2021;99:skab287.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Lim SH, Lee HS, Han H-K, Choi C-I. Saikosaponin A and D inhibit adipogenesis via the AMPK and MAPK signaling pathways in 3T3-L1 adipocytes. Int J Mol Sci. 2021;22:11409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013;417:80–4.

    Article  CAS  PubMed  Google Scholar 

  116. Kumar N, Sharma N, Mehan S. Connection between JAK/STAT and PPARγ signaling during the progression of multiple sclerosis: insights into the modulation of T-cells and immune responses in the brain. Curr Mol Pharmacol. 2021;14:823–37.

    Article  CAS  PubMed  Google Scholar 

  117. Yi L, Zhou X, Li T, Liu P, Hai L, Tong L, et al. Notch1 signaling pathway promotes invasion, self-renewal and growth of glioma initiating cells via modulating chemokine system CXCL12/CXCR4. J Exp Clin Cancer Res. 2019;38:339.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Varshney P, Narasimhan A, Mittal S, Malik G, Sardana K, Saini N. Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis. Sci Rep. 2016;6:19295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sun R, Fang P, Jiang J, Huang C, Wang J, Guo Q, et al. Insulin rescued MCP-1-suppressed cholesterol efflux to large HDL2 particles via ABCA1, ABCG1, SR-BI and PI3K/Akt activation in adipocytes. Cardiovasc Drugs Ther. 2022;36:665–78.

    Article  CAS  PubMed  Google Scholar 

  120. Tsun JGS, Yung S, Chau MKM, Shiu SWM, Chan TM, Tan KCB. Cellular cholesterol transport proteins in diabetic nephropathy. PLoS ONE. 2014;9: e105787.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Kalaany NY, Mangelsdorf DJ. LXRS AND FXR: the Yin and Yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006;68:159–91.

    Article  CAS  PubMed  Google Scholar 

  122. Heller JJ, Qiu J, Zhou L. Nuclear receptors take center stage in Th17 cell–mediated autoimmunity. J Clin Investig. 2011;121:519–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Qian Y, Xia L, Wei L, Jiang W. Artesunate attenuates foam cell formation by enhancing cholesterol efflux. Ann Transl Med. 2021;9:1379–1379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Guccione E, Richard S. The regulation, functions and clinical relevance of arginine methylation. Nat Rev Mol Cell Biol. 2019;20:642–57.

    Article  CAS  PubMed  Google Scholar 

  125. Yuan H, Zhao M, Zhao L, Yun H, Yang G, Geng Y, et al. PRMT5 confers lipid metabolism reprogramming, tumour growth and metastasis depending on the SIRT7-mediated desuccinylation of PRMT5 K387 in tumours. Acta Pharmacol Sin. 2022;43:2373–85.

    Article  CAS  PubMed  Google Scholar 

  126. Webb LM, Sengupta S, Edell C, Piedra-Quintero ZL, Amici SA, Miranda JN, et al. Protein arginine methyltransferase 5 promotes cholesterol biosynthesis–mediated Th17 responses and autoimmunity. J Clin Investig. 2020;130:1683–98.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Lewis BW, Amici SA, Kim H-Y, Shalosky EM, Khan AQ, Walum J, et al. PRMT5 in T cells drives Th17 responses, mixed granulocytic inflammation, and severe allergic airway inflammation. J Immunol. 2022;208:1525–33.

    Article  CAS  PubMed  Google Scholar 

  128. Han C, Ge M, Ho P-C, Zhang L. Fueling T-cell antitumor immunity: amino acid metabolism revisited. Cancer Immunol Res. 2021;9:1373–82.

    Article  CAS  PubMed  Google Scholar 

  129. Johnson MO, Wolf MM, Madden MZ, Andrejeva G, Sugiura A, Contreras DC, et al. Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism. Cell. 2018;175:1780-1795.e19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Yu Q, Tu H, Yin X, Peng C, Dou C, Yang W, et al. Targeting glutamine metabolism ameliorates autoimmune hepatitis via inhibiting T cell activation and differentiation. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.880262.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Lian G, Gnanaprakasam JR, Wang T, Wu R, Chen X, Liu L, et al. Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. Elife. 2018. https://doi.org/10.7554/eLife.36158.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Nakaya M, Xiao Y, Zhou X, Chang J-H, Chang M, Cheng X, et al. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity. 2014;40:692–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Amaya ML, Inguva A, Pei S, Jones C, Krug A, Ye H, et al. The STAT3-MYC axis promotes survival of leukemia stem cells by regulating SLC1A5 and oxidative phosphorylation. Blood. 2022;139:584–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Spiljar M, Kuchroo VK. Metabolic regulation and function of T helper cells in neuroinflammation. Semin Immunopathol. 2022;44:581–98.

    Article  CAS  PubMed  Google Scholar 

  135. Ren W, Liu G, Yin J, Tan B, Wu G, Bazer FW, et al. Amino-acid transporters in T-cell activation and differentiation. Cell Death Dis. 2017;8:e2655–e2655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Albrecht J, Zielińska M. Exchange-mode glutamine transport across CNS cell membranes. Neuropharmacology. 2019;161: 107560.

    Article  CAS  PubMed  Google Scholar 

  137. Suzuki S, Venkatesh D, Kanda H, Nakayama A, Hosokawa H, Lee E, et al. GLS2 is a tumor suppressor and a regulator of ferroptosis in hepatocellular carcinoma. Cancer Res. 2022;82:3209–22.

    Article  CAS  PubMed  Google Scholar 

  138. Yang L, Zheng Y, Miao Y, Yan W, Geng Y, Dai Y, et al. Bergenin, a PPARγ agonist, inhibits Th17 differentiation and subsequent neutrophilic asthma by preventing GLS1-dependent glutaminolysis. Acta Pharmacol Sin. 2022;43:963–76.

    Article  CAS  PubMed  Google Scholar 

  139. Xia X, Cao G, Sun G, Zhu L, Tian Y, Song Y, et al. GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis. J Clin Investig. 2020;130:5180–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Kono M, Yoshida N, Maeda K, Tsokos GC. Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells. Proc Natl Acad Sci. 2018;115:2478–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Feng M, Xiong G, Cao Z, Yang G, Zheng S, Qiu J, et al. LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer. J Exp Clin Cancer Res. 2018;37:274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Zhang X, Wang G, Bi Y, Jiang Z, Wang X. Inhibition of glutaminolysis ameliorates lupus by regulating T and B cell subsets and downregulating the mTOR/P70S6K/4EBP1 and NLRP3/caspase-1/IL-1β pathways in MRL/lpr mice. Int Immunopharmacol. 2022;112: 109133.

    Article  CAS  PubMed  Google Scholar 

  143. Bodineau C, Tomé M, del Murdoch PS, Duran RV. Glutamine, MTOR and autophagy: a multiconnection relationship. Autophagy. 2022;18:2749–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Jeon S-W, Conejos JR, Kim J, Kim M-J, Lee J-E, Lee B-S, et al. Supplementing conjugated and non-conjugated L-methionine and acetate alters expression patterns of CSN2, proteins and metabolites related to protein synthesis in bovine mammary cells. J Dairy Res. 2020;87:70–7.

    Article  CAS  PubMed  Google Scholar 

  145. Pettit AP, Jonsson WO, Bargoud AR, Mirek ET, Peelor FF, Wang Y, et al. Dietary methionine restriction regulates liver protein synthesis and gene expression independently of eukaryotic initiation factor 2 phosphorylation in mice. J Nutr. 2017;147:1031–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Simile MM, Banni S, Angioni E, Carta G, de Miglio MR, Muroni MR, et al. 5′-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication. J Hepatol. 2001;34:386–94.

    Article  CAS  PubMed  Google Scholar 

  147. Panza F, Frisardi V, Capurso C, D’Introno A, Colacicco AM, Vendemiale G, et al. Possible role of S-adenosylmethionine, S-adenosylhomocysteine, and polyunsaturated fatty acids in predementia syndromes and Alzheimer’s disease. J Alzheimer’s Dis. 2009;16:467–70.

    Article  CAS  Google Scholar 

  148. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S-H, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Qi L, Martin-Sandoval MS, Merchant S, Gu W, Eckhardt M, Mathews TP, et al. Aspartate availability limits hematopoietic stem cell function during hematopoietic regeneration. Cell Stem Cell. 2021;28:1982-1999.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM, Martínez-Reyes I, et al. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature. 2019;565:495–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Miao Y, Zheng Y, Geng Y, Yang L, Cao N, Dai Y, et al. The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists. Theranostics. 2021;11:4531–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the National Nature Science Foundation of China (81860726), the Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project (S2019059).

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  1. College of Stomatology, Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China

    Kun Chen, Liying Tang & Xiaolin Nong

  2. Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Xiaolin Nong

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Nong had the idea for the article and critically revised the work. Chen performed the literature search and wrote the main manuscript. Tang created Figs. 1, 2, 3, 4 and modified the text format. Chen and Tang have the same contribution to the article, so they are the co-first authors. All authors read and approved the final manuscript.

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Correspondence to Xiaolin Nong.

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Chen, K., Tang, L. & Nong, X. Artesunate targets cellular metabolism to regulate the Th17/Treg cell balance. Inflamm. Res. 72, 1037–1050 (2023). https://doi.org/10.1007/s00011-023-01729-9

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