Triptolide inhibits Th17 differentiation via controlling PKM2-mediated glycolysis in rheumatoid arthritis

References

• McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–2219.
   PubMed Web of Science ®Google Scholar
• Yang J, Sundrud MS, Skepner J, et al. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci. 2014;35(10):493–500.
   PubMed Web of Science ®Google Scholar
• Zizzo G, De Santis M, Bosello SL, et al. Synovial fluid-derived T helper 17 cells correlate with inflammatory activity in arthritis, irrespectively of diagnosis. Clin Immunol. 2011;138(1):107–116.
   PubMed Web of Science ®Google Scholar
• Kuca-Warnawin E, Kurowska W, Prochorec-Sobieszek M, et al. Rheumatoid arthritis bone marrow environment supports Th17 response. Arthritis Res Ther. 2017;19(1):274.
   PubMedGoogle Scholar
• Yang P, Qian FY, Zhang MF, et al. Th17 cell pathogenicity and plasticity in rheumatoid arthritis. J Leukoc Biol. 2019;106(6):1233–1240.
   PubMed Web of Science ®Google Scholar
• Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity 2009;30(5):646–655.
   PubMed Web of Science ®Google Scholar
• Levescot A, Nelson-Maney N, Morris A, et al. Autoimmune arthritis in IL-1 receptor antagonist-deficient mice is associated with a pathogenic conversion of Foxp3 + regulatory T cells into Th17 cells. Arthritis Rheumatol. 2017;69(10):2712.
   Google Scholar
• Komuczki J, Tuzlak S, Friebel E, et al. Fate-Mapping of GM-CSF expression identifies a discrete subset of inflammation-driving T helper cells regulated by cytokines IL-23 and IL-1β. Immunity. 2019;50(5):1289–1304 e6.
   PubMed Web of Science ®Google Scholar
• Freitag J, Berod L, Kamradt T, et al. Immunometabolism and autoimmunity. Immunol Cell Biol. 2016;94(10):925–934.
   PubMed Web of Science ®Google Scholar
• Buck MD, O'Sullivan D, Pearce EL. T cell metabolism drives immunity. J Exp Med. 2015;212(9):1345–1360.
   PubMed Web of Science ®Google Scholar
• Shi LZ, Wang R, Huang G, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and TREG cells. J Exp Med. 2011;208(7):1367–1376.
   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.
   PubMed Web of Science ®Google Scholar
• Wu L, Hollinshead KER, Hao Y, et al. Niche-Selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy. Cell. 2020;182(3):641–654 e20.
   PubMed Web of Science ®Google Scholar
• Gupta V, Bamezai RN. Human pyruvate kinase M2: a multifunctional protein. Protein Sci. 2010;19(11):2031–2044.
   PubMed Web of Science ®Google Scholar
• Zhang X, Yang Y, Jing L, et al. Pyruvate kinase M2 contributes to TLR-mediated inflammation and autoimmunity by promoting Pyk2 activation. Front Immunol. 2021;12:680068.
   PubMed Web of Science ®Google Scholar
• Angiari S, Runtsch MC, Sutton CE, et al. Pharmacological activation of pyruvate kinase M2 inhibits CD4+ T cell pathogenicity and suppresses autoimmunity. Cell Metab. 2020;31(2):391–405 e8.
   PubMed Web of Science ®Google Scholar
• Damasceno LEA, Prado DS, Veras FP, et al. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J Exp Med. 2020;217(10):e20190613.
   PubMed Web of Science ®Google Scholar
• Kono M, Maeda K, Stocton-Gavanescu I, et al. Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. JCI Insight. 2019;4(12):e127395.
   PubMed Web of Science ®Google Scholar
• Mosure SA, Solt LA. Uncovering new challenges in targeting glycolysis to treat Th17 cell-mediated autoimmunity. Immunometabolism. 2021;3(1):e210006.
   PubMedGoogle Scholar
• Jiang S. Tetrameric PKM2 activation curbs CD4+ T cell overactivation. Trends Endocrinol Metab. 2020;31(6):393–395.
   PubMed Web of Science ®Google Scholar
• Xu J, Jiang C, Wang X, et al. Upregulated PKM2 in macrophages exacerbates experimental arthritis via STAT1 signaling. J Immunol. 2020;205(1):181–192.
   PubMed Web of Science ®Google Scholar
• Pucino V, Certo M, Bulusu V, et al. Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4+ T cell metabolic rewiring. Cell Metab. 2019;30(6):1055–1074.e8.
   PubMed Web of Science ®Google Scholar
• Bao J, Dai SM. A Chinese herb Tripterygium Wilfordii hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety. Rheumatol Int. 2011;31(9):1123–1129.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Mao X, Li W, et al. Tripterygium wilfordii: an inspiring resource for rheumatoid arthritis treatment. Med Res Rev. 2021;41(3):1337–1374.
   PubMed Web of Science ®Google Scholar
• Yu GM, Zhou LF, Zeng BX, et al. The antioxidant effect of triptolide contributes to the therapy in a collagen-induced arthritis rat model. Redox Rep. 2021;26(1):197–202.
   PubMed Web of Science ®Google Scholar
• Song XQ, Zhang Y, Dai EQ, et al. Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and molecular docking. Int Immunopharmacol. 2020;80:106179.
   PubMed Web of Science ®Google Scholar
• Huang J, Zhou L, Wu H, et al. Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-κB activation and titanium particle-induced osteolysis in a mouse model. Mol Cell Endocrinol. 2015;399:346–353.
   PubMed Web of Science ®Google Scholar
• Huang G, Yuan K, Zhu Q, et al. Triptolide inhibits the inflammatory activities of neutrophils to ameliorate chronic arthritis. Mol Immunol. 2018;101:210–220.
   PubMed Web of Science ®Google Scholar
• Yang P, Zhang M, Wang X, et al. MicroRNA let-7g-5p alleviates murine collagen-induced arthritis by inhibiting Th17 cell differentiation. Biochem Pharmacol. 2020;174:113822.
   PubMed Web of Science ®Google Scholar
• Alam J, Jantan I, Bukhari SNA. Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed Pharmacother. 2017;92:615–633.
   PubMed Web of Science ®Google Scholar
• Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet. 2017;389(10086):2338–2348.
   PubMed Web of Science ®Google Scholar
• Law ST, Taylor PC. Role of biological agents in treatment of rheumatoid arthritis. Pharmacol Res. 2019;150:104497.
   PubMed Web of Science ®Google Scholar
• Lv QW, Zhang W, Shi Q, et al. Comparison of Tripterygium Wilfordii hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial. Ann Rheum Dis. 2015;74(6):1078–1086.
   PubMed Web of Science ®Google Scholar
• Wang HL, Jiang Q, Feng XH, et al. Tripterygium wilfordii hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis. BMC Complement Altern Med. 2016;16:215.
   PubMed Web of Science ®Google Scholar
• Liu C, Zhang Y, Kong X, et al. Triptolide prevents bone destruction in the Collagen-Induced arthritis model of rheumatoid arthritis by targeting RANKL/RANK/OPG signal pathway. Evid Based Complement Alternat Med. 2013;2013:626038.
   PubMed Web of Science ®Google Scholar
• Fan D, He X, Bian Y, et al. Triptolide modulates TREM-1 signal pathway to inhibit the inflammatory response in rheumatoid arthritis. Int J Mol Sci. 2016;17(4):498.
   PubMed Web of Science ®Google Scholar
• Li Y, Yu C, Zhu WM, et al. Triptolide ameliorates IL-10-deficient mice colitis by mechanisms involving suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17. Mol Immunol. 2010;47(15):2467–2474.
   PubMed Web of Science ®Google Scholar
• Wu Y, Wang Y, Zhong C, et al. The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response. Int Immunopharmacol. 2003;3(10–11):1457–1465.
   PubMed Web of Science ®Google Scholar
• Wang Y, Jia L, Wu CY. Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis. Scand J Immunol. 2008;68(4):383–390.
   PubMed Web of Science ®Google Scholar
• Karmaus PWF, Chen X, Lim SA, et al. Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity. Nature. 2019;565(7737):101–105.
   PubMed Web of Science ®Google Scholar
• Zuo J, Tang J, Lu M, et al. Glycolysis rate-limiting enzymes: novel potential regulators of rheumatoid arthritis pathogenesis. Front Immunol. 2021;12:779787.
   PubMed Web of Science ®Google Scholar
• Ning XL, Qi HL, Li RD, et al. Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase. Eur J Med Chem. 2017;138:343–352.
   PubMed Web of Science ®Google Scholar
• Zhang YH, Tang YR, Luo YP, et al. Triptolide impairs glycolysis by suppressing GATA4/Sp1/PFKP signaling axis in mouse sertoli cells. Toxicol Appl Pharmacol. 2021;425:115606.
   PubMed Web of Science ®Google Scholar