Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Immunometabolism Dysfunction in the Pathophysiology and Treatment of Rheumatoid Arthritis

Author(s): Maryam Masoumi, Nader Hashemi, Fatemeh Moadab, Mojtaba Didehdar, Rahim Farahani, Hossein Khorramdelazad, Amirhossein Sahebkar*, Thomas P. Johnston and Jafar Karami*

Volume 30, Issue 27, 2023

Published on: 10 November, 2022

Page: [3119 - 3136] Pages: 18

DOI: 10.2174/0929867329666220907151213

Price: $65

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint damage. Systemic complications and progressive disability are burdens that lead to a significant socio-economic costs in patients with RA. Current RA biomarkers used in predicting, diagnosing, and monitoring the treatment of the disease have not been very successful. Moreover, only 60% of patients show a satisfactory response to current biological and conventional therapies. Studies on immunometabolism have suggested that dysregulated enzymes, transcription factors, metabolites, and metabolic pathways could be considered potential therapeutic targets for the treatment of RA. Factors such as the high concentration of various intermediate molecules arising from metabolism, hypoxia, lack of nutrients, and other metabolic alterations affect local immune responses and preserve a state of chronic inflammation in synovial tissues. Fortunately, in vitro and in vivo studies have shown that targeting specific metabolic pathways is associated with a decreased level of inflammation. Specifically, targeting metabolic intermediates, such as succinate or lactate, has shown promising clinical outcomes in RA treatment. These findings open an avenue for the identification of novel biomarkers for diagnosis, prognosis, and determining the success of various treatments in RA patients, as well as the discovery of new therapeutic targets.

Keywords: Rheumatoid, Arthritis, Immunometabolism, Chronic, Inflammation, Treatment

« Previous Next »
[1]
Moadab, F.; Khorramdelazad, H.; Abbasifard, M. Role of CCL2/CCR2 axis in the "immunopathogenesis" of rheumatoid arthritis: Latest evidence and therapeutic approaches. Life Sci., 2021, 269, 119034.
[http://dx.doi.org/10.1016/j.lfs.2021.119034] [PMID: 33453247]
[2]
Karami, J.; Aslani, S.; Tahmasebi, M.N.; Mousavi, M.J.; Sharafat Vaziri, A.; Jamshidi, A.; Farhadi, E.; Mahmoudi, M. Epigenetics in rheumatoid arthritis; fibroblast‐like synoviocytes as an emerging paradigm in the pathogenesis of the disease. Immunol. Cell Biol., 2020, 98(3), 171-186.
[http://dx.doi.org/10.1111/imcb.12311] [PMID: 31856314]
[3]
Dennis, G., Jr; Holweg, C.T.J.; Kummerfeld, S.K.; Choy, D.F.; Setiadi, A.F.; Hackney, J.A.; Haverty, P.M.; Gilbert, H.; Lin, W.Y.; Diehl, L.; Fischer, S.; Song, A.; Musselman, D.; Klearman, M.; Gabay, C.; Kavanaugh, A.; Endres, J.; Fox, D.A.; Martin, F.; Townsend, M.J. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res. Ther., 2014, 16(2), R90.
[http://dx.doi.org/10.1186/ar4555] [PMID: 25167216]
[4]
McInnes, I.B.; Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med., 2011, 365(23), 2205-2219.
[http://dx.doi.org/10.1056/NEJMra1004965] [PMID: 22150039]
[5]
Humby, F.; Lewis, M.; Ramamoorthi, N.; Hackney, J.A.; Barnes, M.R.; Bombardieri, M.; Setiadi, A.F.; Kelly, S.; Bene, F.; DiCicco, M.; Riahi, S.; Rocher, V.; Ng, N.; Lazarou, I.; Hands, R.; van der Heijde, D.; Landewé, R.B.M.; van der Helm-van Mil, A.; Cauli, A.; McInnes, I.; Buckley, C.D.; Choy, E.H.; Taylor, P.C.; Townsend, M.J.; Pitzalis, C. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann. Rheum. Dis., 2019, 78(6), 761-772.
[http://dx.doi.org/10.1136/annrheumdis-2018-214539] [PMID: 30878974]
[6]
Meehan, G.R.; Thomas, R.; Al Khabouri, S.; Wehr, P.; Hilkens, C.M.U.; Wraith, D.C.; Sieghart, D.; Bonelli, M.; Nagy, G.; Garside, P.; Tough, D.F.; Lewis, H.D.; Brewer, J.M. Preclinical models of arthritis for studying immunotherapy and immune tolerance. Ann. Rheum. Dis., 2021, 80(10), 1268-1277.
[http://dx.doi.org/10.1136/annrheumdis-2021-220043] [PMID: 34380700]
[7]
Smolen, J.; Aletaha, D.; McInnes, I. Therapies for bone R. Lancet, 2016, 30173-30178.
[8]
Croft, A.P.; Campos, J.; Jansen, K.; Turner, J.D.; Marshall, J.; Attar, M.; Savary, L.; Wehmeyer, C.; Naylor, A.J.; Kemble, S.; Begum, J.; Dürholz, K.; Perlman, H.; Barone, F.; McGettrick, H.M.; Fearon, D.T.; Wei, K.; Raychaudhuri, S.; Korsunsky, I.; Brenner, M.B.; Coles, M.; Sansom, S.N.; Filer, A.; Buckley, C.D. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature, 2019, 570(7760), 246-251.
[http://dx.doi.org/10.1038/s41586-019-1263-7] [PMID: 31142839]
[9]
Goetzi, E.J.; Falchuk, K.H.; Zeiger, L.S.; Sullivan, A.L.; Hebert, C.L.; Adams, J.P.; Decker, J.L. A physiological approach to the assessment of disease activity in rheumatoid arthritis. J. Clin. Invest., 1971, 50(6), 1167-1180.
[http://dx.doi.org/10.1172/JCI106594] [PMID: 5578228]
[10]
Treuhaft, P.S.; McCarty, D.J. Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum., 1971, 14(4), 475-484.
[http://dx.doi.org/10.1002/art.1780140407] [PMID: 5564921]
[11]
Patella, F.; Schug, Z.T.; Persi, E.; Neilson, L.J.; Erami, Z.; Avanzato, D.; Maione, F.; Hernandez-Fernaud, J.R.; Mackay, G.; Zheng, L.; Reid, S.; Frezza, C.; Giraudo, E.; Fiorio Pla, A.; Anderson, K.; Ruppin, E.; Gottlieb, E.; Zanivan, S. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol. Cell. Proteomics, 2015, 14(3), 621-634.
[http://dx.doi.org/10.1074/mcp.M114.045575] [PMID: 25573745]
[12]
Smolen, J.S.; Breedveld, F.C.; Burmester, G.R.; Bykerk, V.; Dougados, M.; Emery, P.; Kvien, T.K.; Navarro-Compán, M.V.; Oliver, S.; Schoels, M.; Scholte-Voshaar, M.; Stamm, T.; Stoffer, M.; Takeuchi, T.; Aletaha, D.; Andreu, J.L.; Aringer, M.; Bergman, M.; Betteridge, N.; Bijlsma, H.; Burkhardt, H.; Cardiel, M.; Combe, B.; Durez, P.; Fonseca, J.E.; Gibofsky, A.; Gomez-Reino, J.J.; Graninger, W.; Hannonen, P.; Haraoui, B.; Kouloumas, M.; Landewe, R.; Martin-Mola, E.; Nash, P.; Ostergaard, M.; Östör, A.; Richards, P.; Sokka-Isler, T.; Thorne, C.; Tzioufas, A.G.; van Vollenhoven, R.; de Wit, M.; van der Heijde, D. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann. Rheum. Dis., 2016, 75(1), 3-15.
[http://dx.doi.org/10.1136/annrheumdis-2015-207524] [PMID: 25969430]
[13]
Tsokos, GC Metabolic control of arthritis: Switch pathways to treat. Sci. Transl. Med., 2016, 8(331), 331fs8.
[14]
Yang, Z.; Shen, Y.; Oishi, H.; Matteson, E.L.; Tian, L.; Goronzy, J.J. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci. Transl. Med., 2016, 8(331), 331ra38.
[http://dx.doi.org/10.1126/scitranslmed.aad7151]
[15]
Zhou, J.; Chen, J.; Hu, C.; Xie, Z.; Li, H.; Wei, S.; Wang, D.; Wen, C.; Xu, G. Exploration of the serum metabolite signature in patients with rheumatoid arthritis using gas chromatography–mass spectrometry. J. Pharm. Biomed. Anal., 2016, 127, 60-67.
[http://dx.doi.org/10.1016/j.jpba.2016.02.004] [PMID: 26879423]
[16]
Nejatbakhsh Samimi, L.; Farhadi, E.; Tahmasebi, M.N.; Jamshidi, A.; Sharafat Vaziri, A.; Mahmoudi, M. NF-κB signaling in rheumatoid arthritis with focus on fibroblast-like synoviocytes. Auto Immun. Highlights, 2020, 11(1), 11.
[http://dx.doi.org/10.1186/s13317-020-00135-z] [PMID: 32127047]
[17]
Unterberger, S.; Davies, K.A.; Rambhatla, S.B.; Sacre, S. Contribution of toll-like receptors and the NLRP3 inflammasome in rheumatoid arthritis pathophysiology. ImmunoTargets Ther., 2021, 10, 285-298.
[http://dx.doi.org/10.2147/ITT.S288547] [PMID: 34350135]
[18]
Young, S.P.; Kapoor, S.R.; Viant, M.R.; Byrne, J.J.; Filer, A.; Buckley, C.D.; Kitas, G.D.; Raza, K. The impact of inflammation on metabolomic profiles in patients with arthritis. Arthritis Rheum., 2013, 65(8), 2015-2023.
[http://dx.doi.org/10.1002/art.38021] [PMID: 23740368]
[19]
Lauridsen, M.B.; Bliddal, H.; Christensen, R.; Danneskiold-Samsøe, B.; Bennett, R.; Keun, H.; Lindon, J.C.; Nicholson, J.K.; Dorff, M.H.; Jaroszewski, J.W.; Hansen, S.H.; Cornett, C. 1H NMR spectroscopy-based interventional metabolic phenotyping: A cohort study of rheumatoid arthritis patients. J. Proteome Res., 2010, 9(9), 4545-4553.
[http://dx.doi.org/10.1021/pr1002774] [PMID: 20701312]
[20]
Li, J.; Che, N.; Xu, L.; Zhang, Q.; Wang, Q.; Tan, W.; Zhang, M. LC-MS-based serum metabolomics reveals a distinctive signature in patients with rheumatoid arthritis. Clin. Rheumatol., 2018, 37(6), 1493-1502.
[http://dx.doi.org/10.1007/s10067-018-4021-6] [PMID: 29442259]
[21]
Guo, H.; Niu, X.; Gu, Y.; Lu, C.; Xiao, C.; Yue, K.; Zhang, G.; Pan, X.; Jiang, M.; Tan, Y.; Kong, H.; Liu, Z.; Xu, G.; Lu, A. Differential amino acid, carbohydrate and lipid metabolism perpetuations involved in a subtype of rheumatoid arthritis with chinese medicine cold pattern. Int. J. Mol. Sci., 2016, 17(10), 1757.
[http://dx.doi.org/10.3390/ijms17101757] [PMID: 27775663]
[22]
Zabek, A.; Swierkot, J.; Malak, A.; Zawadzka, I.; Deja, S.; Bogunia-Kubik, K.; Mlynarz, P. Application of 1 H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis. J. Pharm. Biomed. Anal., 2016, 117, 544-550.
[http://dx.doi.org/10.1016/j.jpba.2015.10.007] [PMID: 26476882]
[23]
Yang, X.Y.; Zheng, K.D.; Lin, K.; Zheng, G.; Zou, H.; Wang, J.M.; Lin, Y.Y.; Chuka, C.M.; Ge, R.S.; Zhai, W.; Wang, J.G. Energy metabolism disorder as a contributing factor of rheumatoid arthritis: A comparative proteomic and metabolomic study. PLoS One, 2015, 10(7), e0132695.
[http://dx.doi.org/10.1371/journal.pone.0132695] [PMID: 26147000]
[24]
Madsen, R.K.; Lundstedt, T.; Gabrielsson, J.; Sennbro, C.J.; Alenius, G.M.; Moritz, T.; Rantapää-Dahlqvist, S.; Trygg, J. Diagnostic properties of metabolic perturbations in rheumatoid arthritis. Arthritis Res. Ther., 2011, 13(1), R19.
[http://dx.doi.org/10.1186/ar3243] [PMID: 21303541]
[25]
Weyand, C.M.; Zeisbrich, M.; Goronzy, J.J. Metabolic signatures of T-cells and macrophages in rheumatoid arthritis. Curr. Opin. Immunol., 2017, 46, 112-120.
[http://dx.doi.org/10.1016/j.coi.2017.04.010] [PMID: 28538163]
[26]
Pucino, V; Certo, M; Bulusu, V; Cucchi, D; Goldmann, K; Pontarini, E Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4+ T cell metabolic rewiring. Cell metabolism, 2019, 30(6), 1055-74.
[27]
Yang, Z.; Fujii, H.; Mohan, S.V.; Goronzy, J.J.; Weyand, C.M. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J. Exp. Med., 2013, 210(10), 2119-2134.
[http://dx.doi.org/10.1084/jem.20130252] [PMID: 24043759]
[28]
Biniecka, M.; Canavan, M.; McGarry, T.; Gao, W.; McCormick, J.; Cregan, S.; Gallagher, L.; Smith, T.; Phelan, J.J.; Ryan, J.; O’Sullivan, J.; Ng, C.T.; Veale, D.J.; Fearon, U. Dysregulated bioenergetics: A key regulator of joint inflammation. Ann. Rheum. Dis., 2016, 75(12), 2192-2200.
[http://dx.doi.org/10.1136/annrheumdis-2015-208476] [PMID: 27013493]
[29]
Chen, J.; Li, Y.; Tian, Y.; Huang, C.; Li, D.; Zhong, Q.; Ma, X. Interaction between microbes and host intestinal health: Modulation by dietary nutrients and gut-brain-endocrine-immune axis. Curr. Protein Pept. Sci., 2015, 16(7), 592-603.
[http://dx.doi.org/10.2174/1389203716666150630135720] [PMID: 26122779]
[30]
Wen, Z.; Jin, K.; Shen, Y.; Yang, Z.; Li, Y.; Wu, B.; Tian, L.; Shoor, S.; Roche, N.E.; Goronzy, J.J.; Weyand, C.M. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation. Nat. Immunol., 2019, 20(3), 313-325.
[http://dx.doi.org/10.1038/s41590-018-0296-7] [PMID: 30718913]
[31]
Cassano, S.; Pucino, V.; La Rocca, C.; Procaccini, C.; De Rosa, V.; Marone, G.; Matarese, G. Leptin modulates autophagy in human CD4+CD25− conventional T cells. Metabolism, 2014, 63(10), 1272-1279.
[http://dx.doi.org/10.1016/j.metabol.2014.06.010] [PMID: 25060689]
[32]
Falconer, J.; Murphy, A.N.; Young, S.P.; Clark, A.R.; Tiziani, S.; Guma, M.; Buckley, C.D. Synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis Rheumatol., 2018, 70(7), 984-999.
[http://dx.doi.org/10.1002/art.40504] [PMID: 29579371]
[33]
DeLay, M.L.; Turner, M.J.; Klenk, E.I.; Smith, J.A.; Sowders, D.P.; Colbert, R.A. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum., 2009, 60(9), 2633-2643.
[http://dx.doi.org/10.1002/art.24763] [PMID: 19714651]
[34]
Masoumi, M.; Mehrabzadeh, M.; Mahmoudzehi, S.; Mousavi, M.J.; Jamalzehi, S.; Sahebkar, A.; Karami, J. Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis. Int. Immuno- pharmacol., 2020, 89(Pt A), 107064.
[http://dx.doi.org/10.1016/j.intimp.2020.107064] [PMID: 33039953]
[35]
Yarwood, A.; Viatte, S.; Okada, Y.; Plenge, R.; Yamamoto, K.; Barton, A.; Symmons, D.; Raychaudhuri, S.; Klareskog, L.; Gregersen, P.; Worthington, J.; Eyre, S. Loci associated with N-glycosylation of human IgG are not associated with rheumatoid arthritis: A Mendelian randomisation study. Ann. Rheum. Dis., 2016, 75(1), 317-320.
[http://dx.doi.org/10.1136/annrheumdis-2014-207210] [PMID: 26386125]
[36]
Masoumi, M.; Bashiri, H.; Khorramdelazad, H.; Barzaman, K.; Hashemi, N.; Sereshki, H.A. Destructive roles of fibroblast-like synoviocytes in chronic inflammation and joint damage in rheumatoid arthritis. Inflammation, 2020, 1-14.
[PMID: 33113036]
[37]
Okano, T.; Saegusa, J.; Nishimura, K.; Takahashi, S.; Sendo, S.; Ueda, Y.; Morinobu, A. 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation. Sci. Rep., 2017, 7(1), 42412.
[http://dx.doi.org/10.1038/srep42412] [PMID: 28186160]
[38]
Tan, V.P.; Miyamoto, S. HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy, 2015, 11(6), 963-964.
[http://dx.doi.org/10.1080/15548627.2015.1042195] [PMID: 26075878]
[39]
Mousavi, M.J.; Karami, J.; Aslani, S.; Tahmasebi, M.N.; Vaziri, A.S.; Jamshidi, A.; Farhadi, E.; Mahmoudi, M. Transformation of fibroblast-like synoviocytes in rheumatoid arthritis; from a friend to foe. Auto Immun. Highlights, 2021, 12(1), 3.
[http://dx.doi.org/10.1186/s13317-020-00145-x] [PMID: 33546769]
[40]
Biniecka, M.; Connolly, M.; Gao, W.; Ng, C.T.; Balogh, E.; Gogarty, M.; Santos, L.; Murphy, E.; Brayden, D.; Veale, D.J.; Fearon, U. Redox-mediated angiogenesis in the hypoxic joint of inflammatory arthritis. Arthritis Rheumatol., 2014, 66(12), 3300-3310.
[http://dx.doi.org/10.1002/art.38822] [PMID: 25155522]
[41]
Tardito, S.; Martinelli, G.; Soldano, S.; Paolino, S.; Pacini, G.; Patane, M.; Alessandri, E.; Smith, V.; Cutolo, M. Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review. Autoimmun. Rev., 2019, 18(11), 102397.
[http://dx.doi.org/10.1016/j.autrev.2019.102397] [PMID: 31520798]
[42]
Bae, S.; Kim, H.; Lee, N.; Won, C.; Kim, H.R.; Hwang, Y.; Song, Y.W.; Kang, J.S.; Lee, W.J. α-Enolase expressed on the surfaces of monocytes and macrophages induces robust synovial inflammation in rheumatoid arthritis. J. Immunol., 2012, 189(1), 365-372.
[http://dx.doi.org/10.4049/jimmunol.1102073] [PMID: 22623332]
[43]
Moon, J.S.; Hisata, S.; Park, M.A.; DeNicola, G.M.; Ryter, S.W.; Nakahira, K.; Choi, A.M.K. mTORC1-induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation. Cell Rep., 2015, 12(1), 102-115.
[http://dx.doi.org/10.1016/j.celrep.2015.05.046] [PMID: 26119735]
[44]
De Rosa, V.; Galgani, M.; Porcellini, A.; Colamatteo, A.; Santopaolo, M.; Zuchegna, C.; Romano, A.; De Simone, S.; Procaccini, C.; La Rocca, C.; Carrieri, P.B.; Maniscalco, G.T.; Salvetti, M.; Buscarinu, M.C.; Franzese, A.; Mozzillo, E.; La Cava, A.; Matarese, G. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants. Nat. Immunol., 2015, 16(11), 1174-1184.
[http://dx.doi.org/10.1038/ni.3269] [PMID: 26414764]
[45]
Boukouris, A.E.; Zervopoulos, S.D.; Michelakis, E.D. Metabolic enzymes moonlighting in the nucleus: Metabolic regulation of gene transcription. Trends Biochem. Sci., 2016, 41(8), 712-730.
[http://dx.doi.org/10.1016/j.tibs.2016.05.013] [PMID: 27345518]
[46]
Shirai, T.; Nazarewicz, R.R.; Wallis, B.B.; Yanes, R.E.; Watanabe, R.; Hilhorst, M.; Tian, L.; Harrison, D.G.; Giacomini, J.C.; Assimes, T.L.; Goronzy, J.J.; Weyand, C.M. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. J. Exp. Med., 2016, 213(3), 337-354.
[http://dx.doi.org/10.1084/jem.20150900] [PMID: 26926996]
[47]
Lu, Y.; Yu, S.S.; Zong, M.; Fan, S.S.; Lu, T.B.; Gong, R.H.; Sun, L.S.; Fan, L.Y. Glucose-6-phosphate isomerase (G6PI) mediates hypoxia-induced angiogenesis in rheumatoid arthritis. Sci. Rep., 2017, 7(1), 40274.
[http://dx.doi.org/10.1038/srep40274] [PMID: 28067317]
[48]
Thomas, D.P.; Dingle, J.T. In vitro studies of rheumatoid synovium; preliminary metabolic comparison between synovial membrane and villi. Br. J. Exp. Pathol., 1955, 36(2), 195-198.
[PMID: 14363583]
[49]
Bartok, B.; Firestein, G.S. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol. Rev., 2010, 233(1), 233-255.
[http://dx.doi.org/10.1111/j.0105-2896.2009.00859.x] [PMID: 20193003]
[50]
Fujii, W.; Kawahito, Y.; Nagahara, H.; Kukida, Y.; Seno, T.; Yamamoto, A.; Kohno, M.; Oda, R.; Taniguchi, D.; Fujiwara, H.; Ejima, A.; Kishida, T.; Mazda, O.; Ashihara, E. Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis. Arthritis Rheumatol., 2015, 67(11), 2888-2896.
[http://dx.doi.org/10.1002/art.39270] [PMID: 26213210]
[51]
Zhou, R.; Wu, X.; Wang, Z.; Ge, J.; Chen, F. Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes. Int. Immunopharmacol., 2015, 29(2), 748-760.
[http://dx.doi.org/10.1016/j.intimp.2015.08.044] [PMID: 26359543]
[52]
Veras, F.P.; Peres, R.S.; Saraiva, A.L.L.; Pinto, L.G.; Louzada-Junior, P.; Cunha, T.M.; Paschoal, J.A.R.; Cunha, F.Q.; Alves-Filho, J.C. Fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, attenuates experimental arthritis by activating anti-inflammatory adenosinergic pathway. Sci. Rep., 2015, 5(1), 15171.
[http://dx.doi.org/10.1038/srep15171] [PMID: 26478088]
[53]
Haas, R.; Cucchi, D.; Smith, J.; Pucino, V.; Macdougall, C.E.; Mauro, C. Intermediates of metabolism: From bystanders to signalling molecules. Trends Biochem. Sci., 2016, 41(5), 460-471.
[http://dx.doi.org/10.1016/j.tibs.2016.02.003] [PMID: 26935843]
[54]
Narasimhan, R.; Coras, R.; Rosenthal, S.B.; Sweeney, S.R.; Lodi, A.; Tiziani, S.; Boyle, D.; Kavanaugh, A.; Guma, M. Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis. Arthritis Res. Ther., 2018, 20(1), 164.
[http://dx.doi.org/10.1186/s13075-018-1655-3] [PMID: 30075744]
[55]
Jha, A.K.; Huang, S.C.C.; Sergushichev, A.; Lampropoulou, V.; Ivanova, Y.; Loginicheva, E.; Chmielewski, K.; Stewart, K.M.; Ashall, J.; Everts, B.; Pearce, E.J.; Driggers, E.M.; Artyomov, M.N. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity, 2015, 42(3), 419-430.
[http://dx.doi.org/10.1016/j.immuni.2015.02.005] [PMID: 25786174]
[56]
Tannahill, G.M.; Curtis, A.M.; Adamik, J.; Palsson-McDermott, E.M.; McGettrick, A.F.; Goel, G.; Frezza, C.; Bernard, N.J.; Kelly, B.; Foley, N.H.; Zheng, L.; Gardet, A.; Tong, Z.; Jany, S.S.; Corr, S.C.; Haneklaus, M.; Caffrey, B.E.; Pierce, K.; Walmsley, S.; Beasley, F.C.; Cummins, E.; Nizet, V.; Whyte, M.; Taylor, C.T.; Lin, H.; Masters, S.L.; Gottlieb, E.; Kelly, V.P.; Clish, C.; Auron, P.E.; Xavier, R.J.; O’Neill, L.A.J. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature, 2013, 496(7444), 238-242.
[http://dx.doi.org/10.1038/nature11986] [PMID: 23535595]
[57]
Saraiva, A.L.; Veras, F.P.; Peres, R.S.; Talbot, J.; Lima, K.A.; Luiz, J.P.; Carballido, J.M.; Cunha, T.M.; Cunha, F.Q.; Ryffel, B.; Alves-Filho, J.C. Succinate receptor deficiency attenuates arthritis by reducing dendritic cell traffic and expansion of Th 17 cells in the lymph nodes. FASEB J., 2018, 32(12), 6550-6558.
[http://dx.doi.org/10.1096/fj.201800285] [PMID: 29894669]
[58]
Littlewood-Evans, A.; Sarret, S.; Apfel, V.; Loesle, P.; Dawson, J.; Zhang, J.; Muller, A.; Tigani, B.; Kneuer, R.; Patel, S.; Valeaux, S.; Gommermann, N.; Rubic-Schneider, T.; Junt, T.; Carballido, J.M. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis. J. Exp. Med., 2016, 213(9), 1655-1662.
[http://dx.doi.org/10.1084/jem.20160061] [PMID: 27481132]
[59]
Li, Y.; Liu, Y.; Wang, C.; Xia, W.R.; Zheng, J.Y.; Yang, J.; Liu, B.; Liu, J.Q.; Liu, L.F. Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1α/VEGF axis. Free Radic. Biol. Med., 2018, 126, 1-14.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.07.009] [PMID: 30030103]
[60]
Mills, E.L.; Ryan, D.G.; Prag, H.A.; Dikovskaya, D.; Menon, D.; Zaslona, Z.; Jedrychowski, M.P.; Costa, A.S.H.; Higgins, M.; Hams, E.; Szpyt, J.; Runtsch, M.C.; King, M.S.; McGouran, J.F.; Fischer, R.; Kessler, B.M.; McGettrick, A.F.; Hughes, M.M.; Carroll, R.G.; Booty, L.M.; Knatko, E.V.; Meakin, P.J.; Ashford, M.L.J.; Modis, L.K.; Brunori, G.; Sévin, D.C.; Fallon, P.G.; Caldwell, S.T.; Kunji, E.R.S.; Chouchani, E.T.; Frezza, C.; Dinkova-Kostova, A.T.; Hartley, R.C.; Murphy, M.P.; O’Neill, L.A. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature, 2018, 556(7699), 113-117.
[http://dx.doi.org/10.1038/nature25986] [PMID: 29590092]
[61]
McGuire, V.A.; Ruiz-Zorrilla Diez, T.; Emmerich, C.H.; Strickson, S.; Ritorto, M.S.; Sutavani, R.V.; Weiβ, A.; Houslay, K.F.; Knebel, A.; Meakin, P.J.; Phair, I.R.; Ashford, M.L.J.; Trost, M.; Arthur, J.S.C. Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation. Sci. Rep., 2016, 6(1), 31159.
[http://dx.doi.org/10.1038/srep31159] [PMID: 27498693]
[62]
Gold, R.; Kappos, L.; Arnold, D.L.; Bar-Or, A.; Giovannoni, G.; Selmaj, K.; Tornatore, C.; Sweetser, M.T.; Yang, M.; Sheikh, S.I.; Dawson, K.T. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med., 2012, 367(12), 1098-1107.
[http://dx.doi.org/10.1056/NEJMoa1114287] [PMID: 22992073]
[63]
Fox, R.J.; Miller, D.H.; Phillips, J.T.; Hutchinson, M.; Havrdova, E.; Kita, M.; Yang, M.; Raghupathi, K.; Novas, M.; Sweetser, M.T.; Viglietta, V.; Dawson, K.T. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N. Engl. J. Med., 2012, 367(12), 1087-1097.
[http://dx.doi.org/10.1056/NEJMoa1206328] [PMID: 22992072]
[64]
Yamaguchi, Y.; Kanzaki, H.; Katsumata, Y.; Itohiya, K.; Fukaya, S.; Miyamoto, Y.; Narimiya, T.; Wada, S.; Nakamura, Y. Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signalling by augmented antioxidation. J. Cell. Mol. Med., 2018, 22(2), 1138-1147.
[PMID: 29063666]
[65]
Cummings, N.A.; Nordby, G.L. Measurement of synovial fluid pH in normal and arthritic knees. Arthritis Rheum., 1966, 9(1), 47-56.
[http://dx.doi.org/10.1002/art.1780090106] [PMID: 4952418]
[66]
Croia, C.; Serafini, B.; Bombardieri, M.; Kelly, S.; Humby, F.; Severa, M.; Rizzo, F.; Coccia, E.M.; Migliorini, P.; Aloisi, F.; Pitzalis, C. Epstein–Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann. Rheum. Dis., 2013, 72(9), 1559-1568.
[http://dx.doi.org/10.1136/annrheumdis-2012-202352] [PMID: 23268369]
[67]
Pucino, V.; Bombardieri, M.; Pitzalis, C.; Mauro, C. Lactate at the crossroads of metabolism, inflammation, and autoimmunity. Eur. J. Immunol., 2017, 47(1), 14-21.
[http://dx.doi.org/10.1002/eji.201646477] [PMID: 27883186]
[68]
Haas, R.; Smith, J.; Rocher-Ros, V.; Nadkarni, S.; Montero-Melendez, T.; D’Acquisto, F.; Bland, E.J.; Bombardieri, M.; Pitzalis, C.; Perretti, M.; Marelli-Berg, F.M.; Mauro, C. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol., 2015, 13(7), e1002202.
[http://dx.doi.org/10.1371/journal.pbio.1002202] [PMID: 26181372]
[69]
Corcoran, S.E.; O’Neill, L.A.J. HIF1α and metabolic reprogramming in inflammation. J. Clin. Invest., 2016, 126(10), 3699-3707.
[http://dx.doi.org/10.1172/JCI84431] [PMID: 27571407]
[70]
Kelly, B.; O’Neill, L.A.J. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res., 2015, 25(7), 771-784.
[http://dx.doi.org/10.1038/cr.2015.68] [PMID: 26045163]
[71]
Weinberg, F.; Chandel, N.S. Mitochondrial metabolism and cancer. Ann. N. Y. Acad. Sci., 2009, 1177(1), 66-73.
[http://dx.doi.org/10.1111/j.1749-6632.2009.05039.x] [PMID: 19845608]
[72]
Kim, S.; Hwang, J.; Xuan, J.; Jung, Y.H.; Cha, H.S.; Kim, K.H. Global metabolite profiling of synovial fluid for the specific diagnosis of rheumatoid arthritis from other inflammatory arthritis. PLoS One, 2014, 9(6), e97501.
[http://dx.doi.org/10.1371/journal.pone.0097501] [PMID: 24887281]
[73]
Salminen, A.; Kaarniranta, K.; Hiltunen, M.; Kauppinen, A. Krebs cycle dysfunction shapes epigenetic landscape of chromatin: Novel insights into mitochondrial regulation of aging process. Cell. Signal., 2014, 26(7), 1598-1603.
[http://dx.doi.org/10.1016/j.cellsig.2014.03.030] [PMID: 24704120]
[74]
Peti-Peterdi, J.; Kishore, B.K.; Pluznick, J.L. Regulation of vascular and renal function by metabolite receptors. Annu. Rev. Physiol., 2016, 78(1), 391-414.
[http://dx.doi.org/10.1146/annurev-physiol-021115-105403] [PMID: 26667077]
[75]
Mills, E.; O’Neill, L.A.J. Succinate: A metabolic signal in inflammation. Trends Cell Biol., 2014, 24(5), 313-320.
[http://dx.doi.org/10.1016/j.tcb.2013.11.008] [PMID: 24361092]
[76]
Contribution of metabolic reprogramming to macrophage plasticity and function. Seminars in immunology. Semin Immunol, 2015, 27(4), 267-75.
[77]
Tretter, L.; Patocs, A.; Chinopoulos, C. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochim. Biophys. Acta Bioenerg., 2016, 1857(8), 1086-1101.
[http://dx.doi.org/10.1016/j.bbabio.2016.03.012] [PMID: 26971832]
[78]
Mills, E.L.; O’Neill, L.A. Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur. J. Immunol., 2016, 46(1), 13-21.
[http://dx.doi.org/10.1002/eji.201445427] [PMID: 26643360]
[79]
Bonnet, C.S.; Williams, A.S.; Gilbert, S.J.; Harvey, A.K.; Evans, B.A.; Mason, D.J. AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis. Ann. Rheum. Dis., 2015, 74(1), 242-251.
[http://dx.doi.org/10.1136/annrheumdis-2013-203670] [PMID: 24130267]
[80]
Da Sylva, T.R.; Connor, A.; Mburu, Y.; Keystone, E.; Wu, G.E. Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes. Arthritis Res., 2005, 7(4), R844-R851.
[http://dx.doi.org/10.1186/ar1752] [PMID: 15987486]
[81]
Harty, L.C.; Biniecka, M.; O’Sullivan, J.; Fox, E.; Mulhall, K.; Veale, D.J.; Fearon, U. Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis. Ann. Rheum. Dis., 2012, 71(4), 582-588.
[http://dx.doi.org/10.1136/annrheumdis-2011-200245] [PMID: 22121133]
[82]
Datta, S.; Kundu, S.; Ghosh, P.; De, S.; Ghosh, A.; Chatterjee, M. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin. Rheumatol., 2014, 33(11), 1557-1564.
[http://dx.doi.org/10.1007/s10067-014-2597-z] [PMID: 24718487]
[83]
Ishibashi, T. Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Curr. Pharm. Des., 2013, 19(35), 6375-6381.
[http://dx.doi.org/10.2174/13816128113199990507] [PMID: 23859555]
[84]
Chimenti, M; Triggianese, P; Conigliaro, P; Candi, E; Melino, G; Perricone, R The interplay between inflammation and metabolism in rheumatoid arthritis. Cell Death Disease, 2015, 6(9), e1887.
[http://dx.doi.org/10.1038/cddis.2015.246]
[85]
Lee, N.K.; Choi, Y.G.; Baik, J.Y.; Han, S.Y.; Jeong, D.; Bae, Y.S.; Kim, N.; Lee, S.Y. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood, 2005, 106(3), 852-859.
[http://dx.doi.org/10.1182/blood-2004-09-3662] [PMID: 15817678]
[86]
Cucchi, D.; Camacho-Muñoz, D.; Certo, M.; Pucino, V.; Nicolaou, A.; Mauro, C. Fatty acids – from energy substrates to key regulators of cell survival, proliferation and effector function. Cell Stress, 2020, 4(1), 9-23.
[http://dx.doi.org/10.15698/cst2020.01.209] [PMID: 31922096]
[87]
Marone, G.; Galdiero, M.R.; Pecoraro, A.; Pucino, V.; Criscuolo, G.; Triassi, M.; Varricchi, G. Prostaglandin D 2 receptor antagonists in allergic disorders: Safety, efficacy, and future perspectives. Expert Opin. Investig. Drugs, 2019, 28(1), 73-84.
[http://dx.doi.org/10.1080/13543784.2019.1555237] [PMID: 30513028]
[88]
Cipolletta, D.; Feuerer, M.; Li, A.; Kamei, N.; Lee, J.; Shoelson, S.E.; Benoist, C.; Mathis, D. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature, 2012, 486(7404), 549-553.
[http://dx.doi.org/10.1038/nature11132] [PMID: 22722857]
[89]
Klotz, L.; Burgdorf, S.; Dani, I.; Saijo, K.; Flossdorf, J.; Hucke, S.; Alferink, J.; Novak, N.; Beyer, M.; Mayer, G.; Langhans, B.; Klockgether, T.; Waisman, A.; Eberl, G.; Schultze, J.; Famulok, M.; Kolanus, W.; Glass, C.; Kurts, C.; Knolle, P.A. The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell–intrinsic fashion and suppresses CNS autoimmunity. J. Exp. Med., 2009, 206(10), 2079-2089.
[http://dx.doi.org/10.1084/jem.20082771] [PMID: 19737866]
[90]
Berger, J.; Moller, D.E. The mechanisms of action of PPARs. Annu. Rev. Med., 2002, 53(1), 409-435.
[http://dx.doi.org/10.1146/annurev.med.53.082901.104018] [PMID: 11818483]
[91]
Park, J.; Kim, M.; Kang, S.G.; Jannasch, A.H.; Cooper, B.; Patterson, J.; Kim, C.H. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway. Mucosal Immunol., 2015, 8(1), 80-93.
[http://dx.doi.org/10.1038/mi.2014.44] [PMID: 24917457]
[92]
Kidani, Y.; Elsaesser, H.; Hock, M.B.; Vergnes, L.; Williams, K.J.; Argus, J.P.; Marbois, B.N.; Komisopoulou, E.; Wilson, E.B.; Osborne, T.F.; Graeber, T.G.; Reue, K.; Brooks, D.G.; Bensinger, S.J. Sterol regulatory element–binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat. Immunol., 2013, 14(5), 489-499.
[http://dx.doi.org/10.1038/ni.2570] [PMID: 23563690]
[93]
Shen, Y.; Wen, Z.; Li, Y.; Matteson, E.L.; Hong, J.; Goronzy, J.J.; Weyand, C.M. Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells. Nat. Immunol., 2017, 18(9), 1025-1034.
[http://dx.doi.org/10.1038/ni.3808] [PMID: 28737753]
[94]
Berod, L.; Friedrich, C.; Nandan, A.; Freitag, J.; Hagemann, S.; Harmrolfs, K.; Sandouk, A.; Hesse, C.; Castro, C.N.; Bähre, H.; Tschirner, S.K.; Gorinski, N.; Gohmert, M.; Mayer, C.T.; Huehn, J.; Ponimaskin, E.; Abraham, W.R.; Müller, R.; Lochner, M.; Sparwasser, T. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med., 2014, 20(11), 1327-1333.
[http://dx.doi.org/10.1038/nm.3704] [PMID: 25282359]
[95]
Perucha, E.; Melchiotti, R.; Bibby, J.A.; Wu, W.; Frederiksen, K.S.; Roberts, C.A.; Hall, Z.; LeFriec, G.; Robertson, K.A.; Lavender, P.; Gerwien, J.G.; Taams, L.S.; Griffin, J.L.; de Rinaldis, E.; van Baarsen, L.G.M.; Kemper, C.; Ghazal, P.; Cope, A.P. The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells. Nat. Commun., 2019, 10(1), 498.
[http://dx.doi.org/10.1038/s41467-019-08332-9] [PMID: 30700717]
[96]
Volchenkov, R.; Dung Cao, M.; Elgstøen, K.B.; Goll, G.L.; Eikvar, K.; Bjørneboe, O.; Bathen, T.F.; Holen, H.L.; Kvien, T.K.; Skålhegg, B.S. Metabolic profiling of synovial tissue shows altered glucose and choline metabolism in rheumatoid arthritis samples. Scand. J. Rheumatol., 2017, 46(2), 160-161.
[http://dx.doi.org/10.3109/03009742.2016.1164242] [PMID: 27098118]
[97]
Ahn, J.K.; Kim, S.; Hwang, J.; Kim, J.; Kim, K.H.; Cha, H.S. GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis. Joint Bone Spine, 2016, 83(6), 707-713.
[http://dx.doi.org/10.1016/j.jbspin.2015.11.009] [PMID: 27133762]
[98]
Seki, M.; Kawai, Y.; Ishii, C.; Yamanaka, T.; Odawara, M.; Inazu, M. Functional analysis of choline transporters in rheumatoid arthritis synovial fibroblasts. Mod. Rheumatol., 2017, 27(6), 995-1003.
[http://dx.doi.org/10.1080/14397595.2017.1280118] [PMID: 28121199]
[99]
Rose, A.J. Amino acid nutrition and metabolism in health and disease. Nutrients, 2019, 11(11), 2623.
[http://dx.doi.org/10.3390/nu11112623]
[100]
Murray, P.J. Amino acid auxotrophy as a system of immunological control nodes. Nat. Immunol., 2016, 17(2), 132-139.
[http://dx.doi.org/10.1038/ni.3323] [PMID: 26784254]
[101]
Singh, V.K.; Mehrotra, S.; Narayan, P.; Pandey, C.M.; Agarwal, S.S. Modulation of autoimmune diseases by nitric oxide. Immunol. Res., 2000, 22(1), 1-20.
[http://dx.doi.org/10.1385/IR:22:1:1] [PMID: 10945224]
[102]
Schroecksnadel, K.; Winkler, C.; Duftner, C.; Wirleitner, B.; Schirmer, M.; Fuchs, D. Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clin. Rheumatol., 2006, 25(3), 334-337.
[http://dx.doi.org/10.1007/s10067-005-0056-6] [PMID: 16261283]
[103]
Forrest, C.M.; Kennedy, A.; Stone, T.W.; Stoy, N.; Darlington, L.G. Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. In: Allegri, G., Costa, C.V.L., Ragazzi, E., Steinhart, H., Varesio, L. Eds., Developments in tryptophan and serotonin metabolism. Advances in experimental medicine and biology; Springer: Boston, MA, 2003; 527, pp. 287-295.
[104]
Cribbs, A.P.; Kennedy, A.; Penn, H.; Read, J.E.; Amjadi, P.; Green, P.; Syed, K.; Manka, S.W.; Brennan, F.M.; Gregory, B.; Williams, R.O. Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter methylation resulting in a failure to activate the indoleamine 2,3-dioxygenase pathway. Arthritis Rheumatol., 2014, 66(9), 2344-2354.
[http://dx.doi.org/10.1002/art.38715] [PMID: 24891289]
[105]
Criado, G.; Šimelyte, E.; Inglis, J.J.; Essex, D.; Williams, R.O. Indoleamine 2,3 dioxygenase-mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis. Arthritis Rheum., 2009, 60(5), 1342-1351.
[http://dx.doi.org/10.1002/art.24446] [PMID: 19404944]
[106]
Chen, S.Y.; Wu, C.L.; Lai, M.D.; Lin, C.C.; Yo, Y.T.; Jou, I.M.; Lee, C.H.; Weng, C.T.; Shiau, A.L.; Wang, C.R. Amelioration of rat collagen-induced arthritis through CD4+ T cells apoptosis and synovial interleukin-17 reduction by indoleamine 2,3-dioxygenase gene therapy. Hum. Gene Ther., 2011, 22(2), 145-154.
[http://dx.doi.org/10.1089/hum.2009.217] [PMID: 20825285]
[107]
Chalise, J.P.; Pallotta, M.T.; Narendra, S.C.; Carlsson, B.; Iacono, A.; Namale, J.; Boon, L.; Grohmann, U.; Magnusson, M. IDO1 and TGF-β mediate protective effects of IFN-α in antigen-induced arthritis. J. Immunol., 2016, 197(8), 3142-3151.
[http://dx.doi.org/10.4049/jimmunol.1502125] [PMID: 27647832]
[108]
Merlo, L.M.F.; Pigott, E.; DuHadaway, J.B.; Grabler, S.; Metz, R.; Prendergast, G.C.; Mandik-Nayak, L. IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis. J. Immunol., 2014, 192(5), 2082-2090.
[http://dx.doi.org/10.4049/jimmunol.1303012] [PMID: 24489090]
[109]
Collison, J. Do you want to treat arthritis? IDO2! Nat. Rev. Rheumatol., 2017, 13(4), 197.
[http://dx.doi.org/10.1038/nrrheum.2017.33] [PMID: 28275264]
[110]
Merlo, L.M.F.; Grabler, S.; DuHadaway, J.B.; Pigott, E.; Manley, K.; Prendergast, G.C.; Laury-Kleintop, L.D.; Mandik-Nayak, L. Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis. Clin. Immunol., 2017, 179, 8-16.
[http://dx.doi.org/10.1016/j.clim.2017.01.016] [PMID: 28223071]
[111]
Chandrasekharan, U.M.; Wang, Z.; Wu, Y.; Wilson Tang, W.H.; Hazen, S.L.; Wang, S.; Husni, M.E. Elevated levels of plasma symmetric dimethylarginine and increased arginase activity as potential indicators of cardiovascular comorbidity in rheumatoid arthritis. Arthritis Res. Ther., 2018, 20(1), 123.
[http://dx.doi.org/10.1186/s13075-018-1616-x] [PMID: 29884228]
[112]
Hannemann, N.; Jordan, J.; Paul, S.; Reid, S.; Baenkler, H.W.; Sonnewald, S.; Bäuerle, T.; Vera, J.; Schett, G.; Bozec, A. The AP-1 transcription factor c-Jun promotes arthritis by regulating cyclooxygenase-2 and arginase-1 expression in macrophages. J. Immunol., 2017, 198(9), 3605-3614.
[http://dx.doi.org/10.4049/jimmunol.1601330] [PMID: 28298526]
[113]
Chen, Z.; Andreev, D.; Oeser, K.; Krljanac, B.; Hueber, A.; Kleyer, A.; Voehringer, D.; Schett, G.; Bozec, A. Th2 and eosinophil responses suppress inflammatory arthritis. Nat. Commun., 2016, 7(1), 11596.
[http://dx.doi.org/10.1038/ncomms11596] [PMID: 27273006]
[114]
Pucino, V.; Certo, M.; Varricchi, G.; Marone, G.; Ursini, F.; Rossi, F.W.; De Paulis, A.; Mauro, C.; Raza, K.; Buckley, C.D. Metabolic checkpoints in rheumatoid arthritis. Front. Physiol., 2020, 11, 347.
[http://dx.doi.org/10.3389/fphys.2020.00347] [PMID: 32362840]
[115]
Shirwany, N.; Zou, M-H. AMPK: A cellular metabolic and redox sensor. A minireview. Front. Biosci., 2014, 19(3), 447-474.
[http://dx.doi.org/10.2741/4218] [PMID: 24389195]
[116]
Thornton, C.C.; Al-Rashed, F.; Calay, D.; Birdsey, G.M.; Bauer, A.; Mylroie, H.; Morley, B.J.; Randi, A.M.; Haskard, D.O.; Boyle, J.J.; Mason, J.C. Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: A novel mechanism for vascular protection in chronic systemic inflammation. Ann. Rheum. Dis., 2016, 75(2), 439-448.
[http://dx.doi.org/10.1136/annrheumdis-2014-206305] [PMID: 25575725]
[117]
Yan, H; Zhou, H-f; Hu, Y; Pham, CT. Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation. J. Rheum. Dis., 2015, 1(1), 5.
[118]
Kang, K.Y.; Kim, Y.K.; Yi, H.; Kim, J.; Jung, H.R.; Kim, I.J.; Cho, J.H.; Park, S.H.; Kim, H.Y.; Ju, J.H. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int. Immunopharmacol., 2013, 16(1), 85-92.
[http://dx.doi.org/10.1016/j.intimp.2013.03.020] [PMID: 23557965]
[119]
Son, H-J; Lee, J; Lee, S-Y; Kim, E-K; Park, M-J; Kim, K-W. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediat. Inflamm., 2014, 2014, 973986.
[120]
Pucino, V.; Lucherini, O.M.; Perna, F.; Obici, L.; Merlini, G.; Cattalini, M.; La Torre, F.; Maggio, M.C.; Lepore, M.T.; Magnotti, F.; Galgani, M.; Galeazzi, M.; Marone, G.; De Rosa, V.; Talarico, R.; Cantarini, L.; Matarese, G. Differential impact of high and low penetrance TNFRSF1A gene mutations on conventional and regulatory CD4 + T cell functions in TNFR1-associated periodic syndrome. J. Leukoc. Biol., 2016, 99(5), 761-769.
[http://dx.doi.org/10.1189/jlb.3A0915-399R] [PMID: 26598380]
[121]
Pollizzi, K.N.; Powell, J.D. Regulation of T cells by mTOR: The known knowns and the known unknowns. Trends Immunol., 2015, 36(1), 13-20.
[http://dx.doi.org/10.1016/j.it.2014.11.005] [PMID: 25522665]
[122]
Delgoffe, G.M.; Powell, J.D. Feeding an army: The metabolism of T cells in activation, anergy, and exhaustion. Mol. Immunol., 2015, 68(2), 492-496.
[http://dx.doi.org/10.1016/j.molimm.2015.07.026] [PMID: 26256793]
[123]
Perl, A. Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases. Nat. Rev. Rheumatol., 2016, 12(3), 169-182.
[http://dx.doi.org/10.1038/nrrheum.2015.172] [PMID: 26698023]
[124]
Kuhnke, A.; Burmester, G.R.; Krauss, S.; Buttgereit, F. Bioenergetics of immune cells to assess rheumatic disease activity and efficacy of glucocorticoid treatment. Ann. Rheum. Dis., 2003, 62(2), 133-139.
[http://dx.doi.org/10.1136/ard.62.2.133] [PMID: 12525382]
[125]
Moreno-Aurioles, V.R.; Sobrino, F. Glucocorticoids inhibit fructose 2,6-bisphosphate synthesis in rat thymocytes. Opposite effect of cycloheximide. Biochim. Biophys. Acta Mol. Cell Res., 1991, 1091(1), 96-100.
[http://dx.doi.org/10.1016/0167-4889(91)90227-O] [PMID: 1995071]
[126]
Cronstein, B.N.; Aune, T.M. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat. Rev. Rheumatol., 2020, 16(3), 145-154.
[http://dx.doi.org/10.1038/s41584-020-0373-9] [PMID: 32066940]
[127]
McGarry, T.; Orr, C.; Wade, S.; Biniecka, M.; Wade, S.; Gallagher, L.; Low, C.; Veale, D.J.; Fearon, U. JAK/STAT blockade alters synovial bioenergetics, mitochondrial function, and proinflammatory mediators in rheumatoid arthritis. Arthritis Rheumatol., 2018, 70(12), 1959-1970.
[http://dx.doi.org/10.1002/art.40569] [PMID: 29790294]
[128]
Ruiz-Limón, P.; Ortega, R.; Arias de la Rosa, I.; Abalos-Aguilera, M.C.; Perez- Sanchez, C.; Jimenez- Gomez, Y.; Peralbo-Santaella, E.; Font, P.; Ruiz-Vilches, D.; Ferrin, G.; Collantes-Estevez, E.; Escudero-Contreras, A.; López- Pedrera, C.; Barbarroja, N. Tocilizumab improves the proatherothrombotic profile of rheumatoid arthritis patients modulating endothelial dysfunction, NETosis, and inflammation. Transl. Res., 2017, 183, 87-103.
[http://dx.doi.org/10.1016/j.trsl.2016.12.003] [PMID: 28027930]
[129]
Gu, J.J.; Singh, A.; Xue, K.; Mavis, C.; Barth, M.; Yanamadala, V.; Lenz, P.; Grau, M.; Lenz, G.; Czuczman, M.S.; Hernandez-Ilizaliturri, F.J. Up-regulation of hexokinase II contributes to rituximab-chemotherapy resistance and is a clinically relevant target for therapeutic development. Oncotarget, 2018, 9(3), 4020-4033.
[http://dx.doi.org/10.18632/oncotarget.23425] [PMID: 29423101]
[130]
Mondanelli, G.; Iacono, A.; Carvalho, A.; Orabona, C.; Volpi, C.; Pallotta, M.T.; Matino, D.; Esposito, S.; Grohmann, U. Amino acid metabolism as drug target in autoimmune diseases. Autoimmun. Rev., 2019, 18(4), 334-348.
[http://dx.doi.org/10.1016/j.autrev.2019.02.004] [PMID: 30797943]
[131]
Kesharwani, D.; Paliwal, R.; Satapathy, T.; Paul, S.D. Rheumatiod arthritis: An updated overview of latest therapy and drug delivery. J. Pharmacopuncture, 2019, 22(4), 210-224.
[http://dx.doi.org/10.3831/KPI.2019.22.029] [PMID: 31970018]
[132]
Nel, H.J.; Malmström, V.; Wraith, D.C.; Thomas, R. Autoantigens in rheumatoid arthritis and the potential for antigen-specific tolerising immunotherapy. Lancet Rheumatol., 2020, 2(11), e712-e723.
[http://dx.doi.org/10.1016/S2665-9913(20)30344-1]
[133]
Ahmed, M.S.; Bae, Y.S. Dendritic cell-based immunotherapy for rheumatoid arthritis: From bench to bedside. Immune Netw., 2016, 16(1), 44-51.
[http://dx.doi.org/10.4110/in.2016.16.1.44] [PMID: 26937231]
[134]
Bustamante, M.F.; Oliveira, P.G.; Garcia-Carbonell, R.; Croft, A.P.; Smith, J.M.; Serrano, R.L.; Sanchez-Lopez, E.; Liu, X.; Kisseleva, T.; Hay, N.; Buckley, C.D.; Firestein, G.S.; Murphy, A.N.; Miyamoto, S.; Guma, M. Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis. Ann. Rheum. Dis., 2018, 77(11), 1636-1643.
[http://dx.doi.org/10.1136/annrheumdis-2018-213103] [PMID: 30061164]
[135]
Certo, M.; Marone, G.; Paulis, A.; Mauro, C.; Pucino, V. Lactate: Fueling the fire starter. Wiley Interdiscip. Rev. Syst. Biol. Med., 2020, 12(3), e1474.
[http://dx.doi.org/10.1002/wsbm.1474] [PMID: 31840439]
[136]
Pucino, V.; Cucchi, D.; Mauro, C. Lactate transporters as therapeutic targets in cancer and inflammatory diseases. Expert Opin. Ther. Targets, 2018, 22(9), 735-743.
[http://dx.doi.org/10.1080/14728222.2018.1511706] [PMID: 30106309]
[137]
Albini, E.; Coletti, A.; Greco, F.; Pallotta, M.T.; Mondanelli, G.; Gargaro, M.; Belladonna, M.L.; Volpi, C.; Bianchi, R.; Grohmann, U.; Macchiarulo, A.; Orabona, C. Identification of a 2-propanol analogue modulating the non-enzymatic function of indoleamine 2,3-dioxygenase 1. Biochem. Pharmacol., 2018, 158, 286-297.
[http://dx.doi.org/10.1016/j.bcp.2018.10.033] [PMID: 30391205]
[138]
Bevaart, L.; Vervoordeldonk, M.J.; Tak, P.P. Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis? Arthritis Rheum., 2010, 62(8), 2192-2205.
[http://dx.doi.org/10.1002/art.27503] [PMID: 20506322]
[139]
Hegen, M.; Keith, J.C., Jr; Collins, M.; Nickerson-Nutter, C.L. Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann. Rheum. Dis., 2008, 67(11), 1505-1515.
[http://dx.doi.org/10.1136/ard.2007.076430] [PMID: 18055474]
[140]
van Vollenhoven, R.F. Sex differences in rheumatoid arthritis: More than meets the eye. BMC Med., 2009, 7(1), 12.
[http://dx.doi.org/10.1186/1741-7015-7-12] [PMID: 19331649]
[141]
Alpízar-Rodríguez, D.; Pluchino, N.; Canny, G.; Gabay, C.; Finckh, A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology, 2017, 56(8), 1254-1263.
[PMID: 27686101]
[142]
Klinge, C.M. Estrogenic control of mitochondrial function. Redox Biol., 2020, 31, 101435.
[http://dx.doi.org/10.1016/j.redox.2020.101435] [PMID: 32001259]
[143]
Cai, Q.; Lin, T.; Kamarajugadda, S.; Lu, J. Regulation of glycolysis and the Warburg effect by estrogen-related receptors. Oncogene, 2013, 32(16), 2079-2086.
[http://dx.doi.org/10.1038/onc.2012.221] [PMID: 22665055]
[144]
Salomon, R.; Kaczorowski, D.; Valdes-Mora, F.; Nordon, R.E.; Neild, A.; Farbehi, N.; Bartonicek, N.; Gallego-Ortega, D. Droplet-based single cell RNAseq tools: A practical guide. Lab Chip, 2019, 19(10), 1706-1727.
[http://dx.doi.org/10.1039/C8LC01239C] [PMID: 30997473]

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy