Modern concepts of the pathogenesis of rheumatoid arthritis.
Keywords:
rheumatoid arthritis, pathogenetic features, autoimmune inflammation, role of hypoxia
Abstract
The review focuses on modern ideas about the pathophysiology of rheumatoid arthritis (RA). The main steps of the autoimmune process are addressed with a consideration of the role of the common epitope in the human leukocyte antigen system as well as the importance of post-translational modification of a number of proteins, primarily citrullination, and also carbamylation and acetylation, in the formation of autoantibodies. The role of antigen-presenting cells, including macrophages, B-lymphocytes, and dendritic cells, in this process is highlighted. The authors discussed the importance of innate and adaptive immune cells, especially B and T cells, changes in their proliferation and differentiation, and the imbalance of helper CD4+T (Th) cells in RA. Also, the focus of this review is the contribution of pro-inflammatory cytokines and chemokines to the development of the inflammatory reaction of the synovial membrane of affected joints. The importance of several transcription factors involved in the intracellular signal transduction and providing the dynamics of autoimmune inflammation is emphasized. It was shown that recruited and resident synovial fibroblasts are significant for the development of proliferative inflammation with the formation of pannus and subsequent effects on the cartilage and bone tissue. The authors described the mechanisms for destruction of these tissues and the role of activated chondrocytes, osteoclasts and intracellular biochemical cascades in maintaining this pathological process. Particular emphasis is placed on the development of local hypoxia as one of the most important factors in the RA pathogenesis. The causes of hypoxia are given along with the special role of the HIF-1α transcription factor and its connection with other participants in the RA pathological process, such as NF-κB, JAK/STAT, PI3K-AKT, and Notch. The energy imbalance under hypoxic conditions induces mitochondrial dysfunction, which is important in the pathogenesis of RA. This will be discussed in the second part of the review.
Downloads
Download data is not yet available.
References
REFERENCES
1. Nasonov E.L. Problems of rheumatoid arthritis. Evolution of the disease. Nauchno-Prakticheskaya Revmatologiya. 2017; 55 (3): 277-94 (in Russian) https://doi.org/10.14412/1995-4484-2017-277-294
2. Nasonov E.L. Modern concept of autoimmunity in rheumatology Nauchno-Prakticheskaya Revmatologiya. 2023; 61 (4): 397-420 (in Russian). https://doi.org/10.47360/1995-4484-2023-397-420
3. Shchendrigin I.N., Lila A.M. Rheumatoid arthritis: historical aspects. Sovremennaya Revma-tologiya. 2023; 17 (2): 116-24 (in Russian). https://doi.org/10.14412/1996-7012-2023-2-116-124
4. Mclnnes I.B., Schett G. The pathogenesis of rheumatoid arthritis. New Engl. J. Med. 2011; 365: 2205-19. https://doi.org/10.1056/NEJMra1004965
5. Alam J., Jantan I., Nasir S., Bukhari A. Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed. Pharmacother. 2017; 92: 615-33. https://doi.org/10.1016/j.biopha.2017.05.055
6. van Delft M.A.M., Huizinga T.W.J. An overview of autoantibodies in rheumatoid arthritis. J. Autoimmun. 2020; 110: 102392. https://doi.org/10.1016/j.jaut.2019.102392
7. Volkov M., van Schie K.A., van der Woude D. Autoantibodies and B cells: the ABC of rheumatoid arthritis pathophysiology. Immunol. Rev. 2020; 294 (1): 148-63. https://doi.org/10.1111/imr.12829
8. Mueller A-L., Payanden Z., Mohammadkhani N., Mubarak S.M.H., Zakeri A., Bahrami A.A. et al. Recent advanced in understanding the pathogenesis of rheumatoid arthritis: new treat-ment strategies. Cells. 2021; 10 (11): 3017. https://doi.org/10.3390/cells10113017
9. Cutolo M., Campitiello R., Gotelli E., Soldano S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front. Immunol. 2022; 13: 867260. https://doi.org/10.3389/fimmu.2022.867260
10. Ding Q., Hu W., Wang R., Yang Q., Zhu M., Li M. et al. Signaling pathways in rheumatoid arthritis: implications for targeted therapy. Signal Transduct. Target. Ther. 2023; 8:68. https://doi.org/10.1038/s41392-023-01331-9
11. Nandakumar K.S., Fang Q., Ågren I.W., Bejmo Z.F. Aberrant activation of immune and non-immune cells contributes to joint inflammation and bone degradation in rheumatoid ar-thritis. Int. J. Mol. Sci. 2023; 24 (21): 15883. https://doi.org/10.3390/ijms242115883
12. Veale D.J., Orr C., Fearon U. Cellular and molecular perspectives in rheumatoid arthritis. Semin. Immunopathol., 2017; 39 (4): 343-54. https://doi.org/10.1007/s00281-017-0633-1
13. Vossenar E.R., van Venrooij W.J. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res. Ther., 2004; 6 (3): 107-11. https://doi.org/10.1186/ar1184
14. Gregersen P.K., Silver J., Winchester R.J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987; 30 (11): 1205-13. https://doi.org/10.1002/art.1780301102
15. Simon G.M., Cheng J., Gordon J.I. Quantitative assessment of the impact of the gut micro-biota on lysine epsilon-acetilation of host proteins using gnotobiotic mice. Proc. Natl. Acad. Sci. USA. 2012; 109 (28): 11133-38. https://doi.org/10.1073/pnas.1208669109
16. Ma K-W., Ma W. YopJ family effectors promote bacterial infection through a unique acetyl-transferase activity. Microbiol. Mol. Biol. Rev. 2016; 80 (4): 1011-27. https://doi.org/10.1128/MMBR.00032-16
17. Nasonov E.L., Aleksandrova E.N., Avdeeva A.S., Rubtsow Yu.P. T regulatory cells in rheumatoid arthritis. Nauchno-Prakticheskaya Revmatologiya . 2014, 52 (4): 430-37 (in Rus-sian). https://doi.org/10.14412/1995-4484-2014-430-437
18. Sun L., Su Y., Jiao A., Wang X., Zhang B. T cells in health and disease. Signal Transduct. Target. Ther. 2023; 8: 235. https://doi.org/10.1038/s41392-023-01471-y
19. Ziyadullaev Sh.Kh., Khydaiberdiev Sh.Sh., Aripova T.U., Rizaev J.A., Kamalov Z.S., Sul-tonov I.I. et al. Immune changes in synovial fluid in rheumatoidal arthritis. Immunologia. 2023; 44 (5): 653-62 (in Russian). https://doi.org/10.33029/1816-2134-2023-44-5-653-662
20. Noack M., Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun. Rev. 2014; 13 (6): 668-77. https://doi.org/10.1016/j.aurev.2013.12.004
21. Yang Y., Zhang X., Xu M., Wu X., Zhao F., Zhao Z. Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect. Int. Immunopharmacol. 2018; 54: 153-62. https://doi.org/10.1016/j.intimp.2017.11.013
22. Zhang Y., Yang M., Xie H., Hong F., Yang S. Role of miRNAs in rheumatoid arthritis ther-apy. Cells. 2023; 12 (13): 1749. https://doi.org/10.3390/cells12131749
23. Zhu M., Ding Q., Lin Z., Fu R., Zhang F., Li Z. et al. New targets and strategies for rheuma-toid arthritis: from signal transduction to epigenetic aspect. Biomolecules. 2023; 13 (5): 766. https://doi.org/10.3390/biom13050766
24. Kerkman P.F., Fabre E., van der Voort E.I.H., Zaldumbide A., Rombouts Y., Rispens T. et al. Identification and characterization of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis. Ann. Rheum. Dis. 2016; 75 (6): 1170-76. https://doi.org/10.1136/annrheumdis-2014-207182
25. Huang Q-Q., Pope R.M. The role of toll-like receptors in rheumatoid arthritis. Curr. Rheu-matol. Rep. 2009; 11 (5): 357-64. https://doi.org/10.1007/s11926-009-0051-z
26. Vincent F.B., Saulep-Easton D., Figgett W.A., Fairfax K.A., Mackay F. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rep. 2013; 24 (3): 203-15. https://doi.org/10.1016/j.cytogfr.2013.04.003
27. Kerkman P.F., Rombouts Y., van der Voort E.I.H., Trouw L.A., Huizinga T.W., Toes R.E.M. et al. Circullating plasmablasts/plasmacells as a source of anticitrullinated protein anti-bodies in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2013; 72 (7): 1259-63. https://doi.org/10.1136/annrheumdis-2012-202893
28. Kerkman P.F., Kempers A.C., van der Voort E.I.H., van Oosterhout M., Huizinga T.W.J., Toes R.E.M. et al. Synovial fluid mononuclear cells provide an environment for long-term sur-vival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies. Ann. Rheum. Dis. 2016; 75 (12): 2201-7. https://doi.org/10.1136/annrheumdis-2015-208554
29. Corsiero E., Bombardieri M., Carlotti E., Pratesi F., Robinson W., Migliorini P. et al. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells re-veal frequent targeting of citrullinated histones of NETs. Ann. Rheum. Dis. 2016; 75 (10): 1866-75. https://doi.org/10.1136/annrheumdis-2015-208356
30. Matsuda K., Shiba N., Hiraoka K. New insights into role of synovial fibroblasts leading to joint destruction in rheumatoid arthritis. Int. J. Mol. Sci. 2023; 24 (6): 5173. https://doi.org/10.3390/ijms24065173
31. Orsini F., Crotti C., Cincinelli G., Di Taranto R., Amati A., Ferrito M. et al. Bone involve-ment in rheumatoid arthritis and spondyloarthritis: an updated review. Biology (Basel). 2023; 12 (10): 1320. https://doi.org/10.3390/biology12101320
32. Tong Y., Li X., Deng Q., Shi J., Feng Y., Bai L. Advances of the small molecule drugs regu-lating fibroblast-like synovial proliferation for rheumatoid arthritis. Front. Pharmacol. 2023; 14: 1230293. https://doi.org/10.3389/fphar.2023.1230293
33. Bosisio D., Ronca R., Salvi V., Presta M., Sozzani S. Dendriting cells in inflammatory angi-ogenesis and lymphangiogenesis. Curr. Opin. Immunol. 2018; 53: 180-6. https://doi.org/10.1016/j.coi.2018.05.011
34. Del Prete A., Salvi V., Soriani A., Laffranchi M., Sozio F., Bosisio D. et al. Dendritic cell subsets in cancer immunity and tumor antigen sensing. Cell. Mol. Immunol. 2023; 20 (5): 432-47. https://doi.org/10.1038/s41423-023-00990-6
35. Zhao F., He Y., Zhao Z., He J., Huang H., Ai K. et al. The Notch signaling-regulated angio-genesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials. Front. Im-munol. 2023; 14: 1272133. https://doi.org/10.3389/fimmu.2023.1272133
36. Wang Y., Chen S., Du K., Liang C., Wang S., Boadi E.O. et al. Traditional herbal medicine: therapeutic potential in rheumatoid arthritis. J. Etnopharmacol. 2021; 279: 114368. https://doi.org/10.1016/j.jep.2021.114368
37. Gravallese E.M., Firestein G.S. Rheumatoid arthritis – common origins, divergent mecha-nisms. N. Engl. J. Med. 2023; 388: 529-42. https://doi.org/10.1056/NEJMra2103726
38. Nygaard G., Firestein G.S. Restoring synovial homeostasis in rheumatoid arthritis by target-ing fibroblast-like synoviocytes. Nat. Rev. Rheumatol. 2020; 16 (6): 316-33. https://doi.org/10.1038/s41584-020-0413-5
39. Li R-L., Duan H-X., Liang Q., Huang Y-L., Wang L-Y., Zhang Q. et al. Targeting matrix metalloproteases: a promising strategy for herbal medicines to treat rheumatoid arthritis. Front. Immunol. 2022; 13: 1046810. https://doi.org/10.3389/fimmu.2022.1046810
40. Pulik Ƶ., Ƶęgosz P., Motyl G. Matrix metalloproteinases in rheumatoid arthritis and osteoar-thritis: a state of the art review. Rheumatologia. 2023; 61 (3): 191-201. https://doi.org/ 10.5114/reum/168503
41. Schett G., Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat. Rev. Rheumatol. 2012; 8 (11): 656-64. https://doi.org/10.1038/nrrheum.2012.153
42. Auréal M., Machuca-Gayet I., Coury F. Rheumatoid arthritis in the view of osteoimmunolo-gy. Biomolecules. 2021; 11 (1): 48. https://doi.org/10.3390/biom11010048
43. Singh S., Singh T.G., Mahajan K., Dhiman S. Medicinal plants used against various inflam-matory biomarkers for the management of rheumatoid arthritis. J. Pharm. Pharmacol. 2020; 72 (10): 1306-27. https://doi.org/10.1111/jph.13326
44. Xu H., Wang W., Liu X., Huang W., Zhu C., Xu Y. et al. Targeting strategies for bone dis-eases: signaling pathways and clinical studies. Signal Transduct. Target. Ther. 2023; 8 (1): 202. https://doi.org/10.1038/s41392-023-01467-8
45. Harre U., Georgess D., Bang H., Bozec A., Axmann R., Ossipova E. et al. Induction of os-teoclastogenesis in bone loss by human autoantibodies against citrullinated vimentin. J. Clin. Invest. 2012; 122 (5): 1791-1802. https://doi.org/10.1172/jci60975
46. Lund-Olesen K. Oxygen tension in synovial fluids. Arthritis Rheum. 1970; 13 (6): 769-76. https://doi.org/10.1002/art.1780130606
47. Semenza G.L. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol. Med. 2001; 7 (8): 345-50. https://doi.org/10.1016/s1471-4914(01)02090-1
48. Biniecka M., Canavan M., McGarry T., Gao W., McCormick J., Cregan S. et al. Dysregulat-ed bioenergetics: a key regulator of joint inflammation. Ann. Rheum. Dis. 2016; 75 (12): 2192-2200. https://doi.org/10.1136/annrheumdis-2015-208476
49. Fearon U., Canavan M., Biniecka M., Veale D.J. Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis. Nat. Rev. Rheumatol. 2016; 12 (7): 385-97. https://doi.org/10.1038/nrrheum.2016.69
50. McGarry T., Biniecka M., Veale D.J., Fearon U. Hypoxia, oxidative stress and inflammation. Free Radic. Biol. Med. 2018; 125: 15-24. https://doi.org/10.1016/j.freeradbiomed.2018.03.042
51. HanlonM.M., Canavan M., Barker B.E., Fearon U. Metabolites as drivers and targets in rheumatoid arthritis. Clin. Exp. Immunol. 2022; 208: 167-80. https://doi.org/10.1093/cei/uxab021
52. Guo X., Chen G. Hypoxia-inducible factor is critical for pathogenesis and regulation of im-mune cell functions in rheumatoid arthritis. Front. Immunol. 2020; 11: 1668. https://doi.org/10.3389/fimmu.2020.01668
53. López-Armada M.J., Fernández-Rodríguez J.A., Blanco F.J. Mitochondrial dysfunction oxi-dative stress in rheumatoid arthritis. Antioxidants. 2022; 11 (6): 1151. https://doi.org/ 10.3390/antiox11061151
54. Jeon C.H., Ahn J-K., Chai J-Y., Kim H.J., Bae E-K., Park S.H. et al. Hypoxia appears at pre-arthritic stage and shows co-localization with early synovial inflammation in collagen induced arthritis. Clin. Exp. Rheumatol. 2008; 26 (4): 646-48.
55. Ryu J-H., Chae C-S., Kwak J-S., Oh H., Shin Y., Huh Y.H. et al. Hypoxia-inducible factor-2α is ann essential catabolic regulator of inflammatory rheumatoid arthritis. PLoS Biol. 2014, 12 (6): e1001881. https://doi.org/10.1371/journal.pbio.1001881
56. Swales C., Athanasou N.A., Knowles H.J. Angiopoietin-like 4 is over-expressed in rheuma-toid arthritis patients: association with pathological bone resorption. PLos One. 2014; 9 (10): e109524. https://doi.org/10.1371/journal.pone.0109524
57. Oliver K.M., Garvey J.F., Ng CT., Veale D.J., Fearon U., Cummins E.P. et al. Hypoxia acti-vates NF-kappa B-dependent gene expression through the canonical signaling pathway. Anti-oxid. Redox Signal. 2009, 11 (9): 2057-64. https://doi.org/ 10.1089/ars.2008.2400
58. Bruning U., Fitzpatrick S.F., Frank T., Birtwistle M., Taylor C.T., Cheong A. NFκB and HIF display synergistic behavior during hypoxic inflammation. Cell. Mol. Life Sci. 2012; 69 (8): 1319-29. https://doi.org/10.1007/s00018-011-0876-2
59. Trebec-Reynolds D.P., Voronov I., Heersche J.N.M., Manolson M.F. VEGF-A expression in osteoclasts is regulated by NF-κappaB induction of HIF-1 alpha. J. Cell. Biochem. 2010; 110 (2): 343-51. https://doi.org/10.1002/jcb.22542
60. Li G., Zhang Y., Qian Y., Zhang H., Guo S., Sunagawa M.et al. Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway. Moll. Immunol. 2013; 53 (3): 227-36. https://doi.org/10.1016/j.molim
61. Gao W., Sweeney C., Connolly M., Kennedy A., Ng C.T., McCormic J. et al. Notch-1 medi-ates hypoxia-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum. 2012; 64 (7): 2104-13. https://doi.org/10.1002/art.34397
62. Chen J., Cheng W., Li J., Wang Y., Chen J., Shen X. et al. Notch-1 and Notch-3 mediate hypoxia-induced activation of synovial fibroblasts in rheumatoid arthritis. Arthritis Rheumatol. 2021; 73 (10): 1810-19. https://doi.org/10.1002/art.41748
63. Gustafsson M.V., Zheng X., Pereira T., Gradin K., Jin S., Lundkvist J. et al. Hypoxia re-quires notch signaling to maintain the undifferentiated cell state. Dev. Cell. 2005; 9 (5): 617-28. https://doi.org/ 10.1016/j.devcel.2005.09.010
64. Malemud C.J. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther. Adv. Musculoskelet. Dis. 2018; 10 (5-6): 117-27. https://doi.org/ 10.1177/1759720x18776224
65. Simon L.S., Taylor P.C., Choy E.H., Sebba A., Quebe A., Knopp K.L. et al. The Jak/STAT pathway: a focus on pain in rheumatoid arthritis. Semin. Arthritis Rheum. 2021; 51 (1): 278-84. https://doi.org/10.1016/j.semarthrit.2020.10.008
66. Hammaker D., Nygaard G., Kuhs A., Ai R., Boyle D.L., Wang W. et al. Joint location-specific JAK-STAT signaling in rheumatoid arthritis fibroblast-like synoviocytes. ACR Open Rheumatol. 2019; 1 (10): 640-48. https://doi.org/10.1002/acr2.11093
67. Emori T., Kasahara M., Sugahara S., Hashimoto M., Ito H., Narumiya S. et al. Role of JAK-STAT signaling in the pathogenic behavior of fibroblast-like synoviocytes in rheumatoid ar-thritis: effect of the novel JAK inhibitor peficitinib. Eur. J. Pharmacol. 2020; 882: 173238. https://doi.org/10.1016/j.ejphar.2020.173238
68. Oike T., Sato Y., Kobayashi T., Miyamoto K., Nakamura S., Kaneko Y. et al. Stat3 as a po-tential therapeutic target for rheumatoid arthritis. Sci. Rep. 2017; 7 (1): 10965. https://doi.org/ 10.1038/s41598-017-11233-w
69. Jung J.E., Lee H.G., Cho I.H., Chung D.H., Yoon S-H., Yang Y.M. et al. STAT3is a poten-tial modulator of HIF-1 mediated VEGF expression in human renal carcinoma cells. FASEB J. 2005; 19 (10): 1296-98. https://doi.org/10.1098/fj.04-3099 fje
70. Jung J.E., Kim H.S., Lee C.S., Shin Y.J., Kim Y.N., Kang G.H. et al. STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubuquitination. Exp. Mol. Med. 2008, 40 (5): 479-85. https://doi.org/10.3858/emm.2008.40.5.
71. Qiang L., Wu T., Zhang H-W., Lu N., Hu R., Wang Y-J. et al. HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ. 2012, 19: 284-94. https://doi.org/10.1038/cdd.2011.95
72. Gao W., McCormick J., Connolly M., Balogh E., Veale D.J., Fearon U. Hypoxia and STAT3 signaling interactions regulate pro-inflammatory pathways in rheumatoid arthritis. Ann. Rheum. Dis. 2015; 74 (6): 1275-83. https://doi.org/10.1136/annrheumdis-2013-204105
73. Li G-Q., Zhang Y., Liu D., Qian Y-Y., Zhang H., Guo S-Y. et al. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol. Cell Biochem. 2013; 372: 221-31. https://doi.org/ 10.1007/s1 1010-012-1463-z
74. Slepneva L.V., Khmylova G.A. Failure mechanism of energy metabolism during hypoxia and possible ways to correlation of fumaratecontaining solutions. Transfusiology. 2013; 14 (2): 49-65 (in Russian).
75. Titova O.N., Kuzubova N.A., Lebedeva E.S. The role of the hypoxia signaling pathway in cellular adaptation to hypoxia. RMZH Medicinskoe obozrenie. 2020; 4 (4): 207-13 (in Rus-sian). https://doi.org/10.32364/2587-6821-2020-4-4-207-213
76. Shime H., Yabu M., Akazawa T., Kodama K., Matsumoto M., Seya T. et al. Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J. Immunol. 2008; 180 (11): 7175-83. https://doi.org/10.4049/jimmunol.180.11.7175
77. Haas R., Smith J., Rocher-Ros V., Nadkarni S., Montero-Melendez T., D’Acquisito F. et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol. 2015; 13 (7): e1002202. https://doi.org/ 10.1371/journal.pbio.1002202
78. Yi O., Lin Y., Hu M., Hu S., Su Z., Liao J. et al. Lactate metabolism in rheumatoid arthritis: pathogenic mechanisms and therapeutic intervention with natural compounds. Phytomedicine. 2022; 100: 154048. https://doi.org/10.1016/j.phymed.2022.154048
79. Makino Y., Nakamura H., Ikeda E., Ohnuma K., Yamauchi K., Yabe Y. et al. Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J. Immunol. 2003, 171 (12): 6534-6540. https://doi.org/10.4049/jimmunol.171.12.6534
80. Gaber T., Hȁupl T., Sandig G., Tykwinska K., Fangradt M., Tschirschmann M. et al. Adap-tation of human CD4 T cells to pathophysiological hypoxia: a transcriptome analysis. J. Rheu-matol. 2009; 36 (12): 2655-69. https://doi.org/10.3899/jrheum.090255
81. Lewis J.S., Lee J.A., Underwood J.C., Harris A.L., Lewis C.E. Macrophage responses to hypoxia: relevance to disease mechanisms. J. Leukoc. Biol. 1999; 66 (6): 889-900. https://doi.org/10.1002/jib.66.6.889
82. Cramer T., Yamanishi Y., Clausen B.E., Förster I., Pawlinski R., Mackman N. et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cells. 2003; 112 (5): 645-57. https://doi.org/10.1016/s0092-8674(03)00154-5
83. Blagih J., Jones R.G. Polarizing macrophages through reprogramming of glucose metabolism. Cell. Metab. 2012; 15 (6): 793-95. https://doi.org/10.1016/j.cmet.2012.05.008
84. Riccardi A., Elia A.R., Cappello P., Puppo M., Vanni C., Fardin P. et al. Transcriptome of hypoxic immature dendrite cells: modulation of chemokine/receptor expression. Mol. Cancer Res. 2008; 6 (2): 175-85. https://doi.org/10.1158/1541-7786.MCR-07-0391
85. Yang M., Ma C., Liu S., Sun J., Shao Q., Gao W. et al. Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype and promotes tumour cell migration by dendritic cell-derived osteopontin. Immunology. 2009, 128 (1 Suppl): e237-49. https://doi.org/10.1111/j.1365-2567.2008.02954.x
86. Mancino A., Schioppa T., Larghi P., Pasqualini F., Nebuloni M., Chen I-H. et al. Divergent effects of hypoxia on dendritic cell functions. Blood. 2008, 112 (9): 3723-34. https://doi.org/10.1182/blood-2008-02-142091
87. Blengio F., Raggi F., Pierobon D., Cappello P., Eva A., Giovarelli M. et al. The hypoxic en-vironment reprograms the cytokine/chemokine expression profile of human mature dendritic cells. Immunology. 2013; 218 (1): 76-89. https://doi.org/10.1016/j.imbio.2012.02.002
1. Nasonov E.L. Problems of rheumatoid arthritis. Evolution of the disease. Nauchno-Prakticheskaya Revmatologiya. 2017; 55 (3): 277-94 (in Russian) https://doi.org/10.14412/1995-4484-2017-277-294
2. Nasonov E.L. Modern concept of autoimmunity in rheumatology Nauchno-Prakticheskaya Revmatologiya. 2023; 61 (4): 397-420 (in Russian). https://doi.org/10.47360/1995-4484-2023-397-420
3. Shchendrigin I.N., Lila A.M. Rheumatoid arthritis: historical aspects. Sovremennaya Revma-tologiya. 2023; 17 (2): 116-24 (in Russian). https://doi.org/10.14412/1996-7012-2023-2-116-124
4. Mclnnes I.B., Schett G. The pathogenesis of rheumatoid arthritis. New Engl. J. Med. 2011; 365: 2205-19. https://doi.org/10.1056/NEJMra1004965
5. Alam J., Jantan I., Nasir S., Bukhari A. Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed. Pharmacother. 2017; 92: 615-33. https://doi.org/10.1016/j.biopha.2017.05.055
6. van Delft M.A.M., Huizinga T.W.J. An overview of autoantibodies in rheumatoid arthritis. J. Autoimmun. 2020; 110: 102392. https://doi.org/10.1016/j.jaut.2019.102392
7. Volkov M., van Schie K.A., van der Woude D. Autoantibodies and B cells: the ABC of rheumatoid arthritis pathophysiology. Immunol. Rev. 2020; 294 (1): 148-63. https://doi.org/10.1111/imr.12829
8. Mueller A-L., Payanden Z., Mohammadkhani N., Mubarak S.M.H., Zakeri A., Bahrami A.A. et al. Recent advanced in understanding the pathogenesis of rheumatoid arthritis: new treat-ment strategies. Cells. 2021; 10 (11): 3017. https://doi.org/10.3390/cells10113017
9. Cutolo M., Campitiello R., Gotelli E., Soldano S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front. Immunol. 2022; 13: 867260. https://doi.org/10.3389/fimmu.2022.867260
10. Ding Q., Hu W., Wang R., Yang Q., Zhu M., Li M. et al. Signaling pathways in rheumatoid arthritis: implications for targeted therapy. Signal Transduct. Target. Ther. 2023; 8:68. https://doi.org/10.1038/s41392-023-01331-9
11. Nandakumar K.S., Fang Q., Ågren I.W., Bejmo Z.F. Aberrant activation of immune and non-immune cells contributes to joint inflammation and bone degradation in rheumatoid ar-thritis. Int. J. Mol. Sci. 2023; 24 (21): 15883. https://doi.org/10.3390/ijms242115883
12. Veale D.J., Orr C., Fearon U. Cellular and molecular perspectives in rheumatoid arthritis. Semin. Immunopathol., 2017; 39 (4): 343-54. https://doi.org/10.1007/s00281-017-0633-1
13. Vossenar E.R., van Venrooij W.J. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res. Ther., 2004; 6 (3): 107-11. https://doi.org/10.1186/ar1184
14. Gregersen P.K., Silver J., Winchester R.J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987; 30 (11): 1205-13. https://doi.org/10.1002/art.1780301102
15. Simon G.M., Cheng J., Gordon J.I. Quantitative assessment of the impact of the gut micro-biota on lysine epsilon-acetilation of host proteins using gnotobiotic mice. Proc. Natl. Acad. Sci. USA. 2012; 109 (28): 11133-38. https://doi.org/10.1073/pnas.1208669109
16. Ma K-W., Ma W. YopJ family effectors promote bacterial infection through a unique acetyl-transferase activity. Microbiol. Mol. Biol. Rev. 2016; 80 (4): 1011-27. https://doi.org/10.1128/MMBR.00032-16
17. Nasonov E.L., Aleksandrova E.N., Avdeeva A.S., Rubtsow Yu.P. T regulatory cells in rheumatoid arthritis. Nauchno-Prakticheskaya Revmatologiya . 2014, 52 (4): 430-37 (in Rus-sian). https://doi.org/10.14412/1995-4484-2014-430-437
18. Sun L., Su Y., Jiao A., Wang X., Zhang B. T cells in health and disease. Signal Transduct. Target. Ther. 2023; 8: 235. https://doi.org/10.1038/s41392-023-01471-y
19. Ziyadullaev Sh.Kh., Khydaiberdiev Sh.Sh., Aripova T.U., Rizaev J.A., Kamalov Z.S., Sul-tonov I.I. et al. Immune changes in synovial fluid in rheumatoidal arthritis. Immunologia. 2023; 44 (5): 653-62 (in Russian). https://doi.org/10.33029/1816-2134-2023-44-5-653-662
20. Noack M., Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun. Rev. 2014; 13 (6): 668-77. https://doi.org/10.1016/j.aurev.2013.12.004
21. Yang Y., Zhang X., Xu M., Wu X., Zhao F., Zhao Z. Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect. Int. Immunopharmacol. 2018; 54: 153-62. https://doi.org/10.1016/j.intimp.2017.11.013
22. Zhang Y., Yang M., Xie H., Hong F., Yang S. Role of miRNAs in rheumatoid arthritis ther-apy. Cells. 2023; 12 (13): 1749. https://doi.org/10.3390/cells12131749
23. Zhu M., Ding Q., Lin Z., Fu R., Zhang F., Li Z. et al. New targets and strategies for rheuma-toid arthritis: from signal transduction to epigenetic aspect. Biomolecules. 2023; 13 (5): 766. https://doi.org/10.3390/biom13050766
24. Kerkman P.F., Fabre E., van der Voort E.I.H., Zaldumbide A., Rombouts Y., Rispens T. et al. Identification and characterization of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis. Ann. Rheum. Dis. 2016; 75 (6): 1170-76. https://doi.org/10.1136/annrheumdis-2014-207182
25. Huang Q-Q., Pope R.M. The role of toll-like receptors in rheumatoid arthritis. Curr. Rheu-matol. Rep. 2009; 11 (5): 357-64. https://doi.org/10.1007/s11926-009-0051-z
26. Vincent F.B., Saulep-Easton D., Figgett W.A., Fairfax K.A., Mackay F. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rep. 2013; 24 (3): 203-15. https://doi.org/10.1016/j.cytogfr.2013.04.003
27. Kerkman P.F., Rombouts Y., van der Voort E.I.H., Trouw L.A., Huizinga T.W., Toes R.E.M. et al. Circullating plasmablasts/plasmacells as a source of anticitrullinated protein anti-bodies in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2013; 72 (7): 1259-63. https://doi.org/10.1136/annrheumdis-2012-202893
28. Kerkman P.F., Kempers A.C., van der Voort E.I.H., van Oosterhout M., Huizinga T.W.J., Toes R.E.M. et al. Synovial fluid mononuclear cells provide an environment for long-term sur-vival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies. Ann. Rheum. Dis. 2016; 75 (12): 2201-7. https://doi.org/10.1136/annrheumdis-2015-208554
29. Corsiero E., Bombardieri M., Carlotti E., Pratesi F., Robinson W., Migliorini P. et al. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells re-veal frequent targeting of citrullinated histones of NETs. Ann. Rheum. Dis. 2016; 75 (10): 1866-75. https://doi.org/10.1136/annrheumdis-2015-208356
30. Matsuda K., Shiba N., Hiraoka K. New insights into role of synovial fibroblasts leading to joint destruction in rheumatoid arthritis. Int. J. Mol. Sci. 2023; 24 (6): 5173. https://doi.org/10.3390/ijms24065173
31. Orsini F., Crotti C., Cincinelli G., Di Taranto R., Amati A., Ferrito M. et al. Bone involve-ment in rheumatoid arthritis and spondyloarthritis: an updated review. Biology (Basel). 2023; 12 (10): 1320. https://doi.org/10.3390/biology12101320
32. Tong Y., Li X., Deng Q., Shi J., Feng Y., Bai L. Advances of the small molecule drugs regu-lating fibroblast-like synovial proliferation for rheumatoid arthritis. Front. Pharmacol. 2023; 14: 1230293. https://doi.org/10.3389/fphar.2023.1230293
33. Bosisio D., Ronca R., Salvi V., Presta M., Sozzani S. Dendriting cells in inflammatory angi-ogenesis and lymphangiogenesis. Curr. Opin. Immunol. 2018; 53: 180-6. https://doi.org/10.1016/j.coi.2018.05.011
34. Del Prete A., Salvi V., Soriani A., Laffranchi M., Sozio F., Bosisio D. et al. Dendritic cell subsets in cancer immunity and tumor antigen sensing. Cell. Mol. Immunol. 2023; 20 (5): 432-47. https://doi.org/10.1038/s41423-023-00990-6
35. Zhao F., He Y., Zhao Z., He J., Huang H., Ai K. et al. The Notch signaling-regulated angio-genesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials. Front. Im-munol. 2023; 14: 1272133. https://doi.org/10.3389/fimmu.2023.1272133
36. Wang Y., Chen S., Du K., Liang C., Wang S., Boadi E.O. et al. Traditional herbal medicine: therapeutic potential in rheumatoid arthritis. J. Etnopharmacol. 2021; 279: 114368. https://doi.org/10.1016/j.jep.2021.114368
37. Gravallese E.M., Firestein G.S. Rheumatoid arthritis – common origins, divergent mecha-nisms. N. Engl. J. Med. 2023; 388: 529-42. https://doi.org/10.1056/NEJMra2103726
38. Nygaard G., Firestein G.S. Restoring synovial homeostasis in rheumatoid arthritis by target-ing fibroblast-like synoviocytes. Nat. Rev. Rheumatol. 2020; 16 (6): 316-33. https://doi.org/10.1038/s41584-020-0413-5
39. Li R-L., Duan H-X., Liang Q., Huang Y-L., Wang L-Y., Zhang Q. et al. Targeting matrix metalloproteases: a promising strategy for herbal medicines to treat rheumatoid arthritis. Front. Immunol. 2022; 13: 1046810. https://doi.org/10.3389/fimmu.2022.1046810
40. Pulik Ƶ., Ƶęgosz P., Motyl G. Matrix metalloproteinases in rheumatoid arthritis and osteoar-thritis: a state of the art review. Rheumatologia. 2023; 61 (3): 191-201. https://doi.org/ 10.5114/reum/168503
41. Schett G., Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat. Rev. Rheumatol. 2012; 8 (11): 656-64. https://doi.org/10.1038/nrrheum.2012.153
42. Auréal M., Machuca-Gayet I., Coury F. Rheumatoid arthritis in the view of osteoimmunolo-gy. Biomolecules. 2021; 11 (1): 48. https://doi.org/10.3390/biom11010048
43. Singh S., Singh T.G., Mahajan K., Dhiman S. Medicinal plants used against various inflam-matory biomarkers for the management of rheumatoid arthritis. J. Pharm. Pharmacol. 2020; 72 (10): 1306-27. https://doi.org/10.1111/jph.13326
44. Xu H., Wang W., Liu X., Huang W., Zhu C., Xu Y. et al. Targeting strategies for bone dis-eases: signaling pathways and clinical studies. Signal Transduct. Target. Ther. 2023; 8 (1): 202. https://doi.org/10.1038/s41392-023-01467-8
45. Harre U., Georgess D., Bang H., Bozec A., Axmann R., Ossipova E. et al. Induction of os-teoclastogenesis in bone loss by human autoantibodies against citrullinated vimentin. J. Clin. Invest. 2012; 122 (5): 1791-1802. https://doi.org/10.1172/jci60975
46. Lund-Olesen K. Oxygen tension in synovial fluids. Arthritis Rheum. 1970; 13 (6): 769-76. https://doi.org/10.1002/art.1780130606
47. Semenza G.L. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol. Med. 2001; 7 (8): 345-50. https://doi.org/10.1016/s1471-4914(01)02090-1
48. Biniecka M., Canavan M., McGarry T., Gao W., McCormick J., Cregan S. et al. Dysregulat-ed bioenergetics: a key regulator of joint inflammation. Ann. Rheum. Dis. 2016; 75 (12): 2192-2200. https://doi.org/10.1136/annrheumdis-2015-208476
49. Fearon U., Canavan M., Biniecka M., Veale D.J. Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis. Nat. Rev. Rheumatol. 2016; 12 (7): 385-97. https://doi.org/10.1038/nrrheum.2016.69
50. McGarry T., Biniecka M., Veale D.J., Fearon U. Hypoxia, oxidative stress and inflammation. Free Radic. Biol. Med. 2018; 125: 15-24. https://doi.org/10.1016/j.freeradbiomed.2018.03.042
51. HanlonM.M., Canavan M., Barker B.E., Fearon U. Metabolites as drivers and targets in rheumatoid arthritis. Clin. Exp. Immunol. 2022; 208: 167-80. https://doi.org/10.1093/cei/uxab021
52. Guo X., Chen G. Hypoxia-inducible factor is critical for pathogenesis and regulation of im-mune cell functions in rheumatoid arthritis. Front. Immunol. 2020; 11: 1668. https://doi.org/10.3389/fimmu.2020.01668
53. López-Armada M.J., Fernández-Rodríguez J.A., Blanco F.J. Mitochondrial dysfunction oxi-dative stress in rheumatoid arthritis. Antioxidants. 2022; 11 (6): 1151. https://doi.org/ 10.3390/antiox11061151
54. Jeon C.H., Ahn J-K., Chai J-Y., Kim H.J., Bae E-K., Park S.H. et al. Hypoxia appears at pre-arthritic stage and shows co-localization with early synovial inflammation in collagen induced arthritis. Clin. Exp. Rheumatol. 2008; 26 (4): 646-48.
55. Ryu J-H., Chae C-S., Kwak J-S., Oh H., Shin Y., Huh Y.H. et al. Hypoxia-inducible factor-2α is ann essential catabolic regulator of inflammatory rheumatoid arthritis. PLoS Biol. 2014, 12 (6): e1001881. https://doi.org/10.1371/journal.pbio.1001881
56. Swales C., Athanasou N.A., Knowles H.J. Angiopoietin-like 4 is over-expressed in rheuma-toid arthritis patients: association with pathological bone resorption. PLos One. 2014; 9 (10): e109524. https://doi.org/10.1371/journal.pone.0109524
57. Oliver K.M., Garvey J.F., Ng CT., Veale D.J., Fearon U., Cummins E.P. et al. Hypoxia acti-vates NF-kappa B-dependent gene expression through the canonical signaling pathway. Anti-oxid. Redox Signal. 2009, 11 (9): 2057-64. https://doi.org/ 10.1089/ars.2008.2400
58. Bruning U., Fitzpatrick S.F., Frank T., Birtwistle M., Taylor C.T., Cheong A. NFκB and HIF display synergistic behavior during hypoxic inflammation. Cell. Mol. Life Sci. 2012; 69 (8): 1319-29. https://doi.org/10.1007/s00018-011-0876-2
59. Trebec-Reynolds D.P., Voronov I., Heersche J.N.M., Manolson M.F. VEGF-A expression in osteoclasts is regulated by NF-κappaB induction of HIF-1 alpha. J. Cell. Biochem. 2010; 110 (2): 343-51. https://doi.org/10.1002/jcb.22542
60. Li G., Zhang Y., Qian Y., Zhang H., Guo S., Sunagawa M.et al. Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway. Moll. Immunol. 2013; 53 (3): 227-36. https://doi.org/10.1016/j.molim
61. Gao W., Sweeney C., Connolly M., Kennedy A., Ng C.T., McCormic J. et al. Notch-1 medi-ates hypoxia-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum. 2012; 64 (7): 2104-13. https://doi.org/10.1002/art.34397
62. Chen J., Cheng W., Li J., Wang Y., Chen J., Shen X. et al. Notch-1 and Notch-3 mediate hypoxia-induced activation of synovial fibroblasts in rheumatoid arthritis. Arthritis Rheumatol. 2021; 73 (10): 1810-19. https://doi.org/10.1002/art.41748
63. Gustafsson M.V., Zheng X., Pereira T., Gradin K., Jin S., Lundkvist J. et al. Hypoxia re-quires notch signaling to maintain the undifferentiated cell state. Dev. Cell. 2005; 9 (5): 617-28. https://doi.org/ 10.1016/j.devcel.2005.09.010
64. Malemud C.J. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther. Adv. Musculoskelet. Dis. 2018; 10 (5-6): 117-27. https://doi.org/ 10.1177/1759720x18776224
65. Simon L.S., Taylor P.C., Choy E.H., Sebba A., Quebe A., Knopp K.L. et al. The Jak/STAT pathway: a focus on pain in rheumatoid arthritis. Semin. Arthritis Rheum. 2021; 51 (1): 278-84. https://doi.org/10.1016/j.semarthrit.2020.10.008
66. Hammaker D., Nygaard G., Kuhs A., Ai R., Boyle D.L., Wang W. et al. Joint location-specific JAK-STAT signaling in rheumatoid arthritis fibroblast-like synoviocytes. ACR Open Rheumatol. 2019; 1 (10): 640-48. https://doi.org/10.1002/acr2.11093
67. Emori T., Kasahara M., Sugahara S., Hashimoto M., Ito H., Narumiya S. et al. Role of JAK-STAT signaling in the pathogenic behavior of fibroblast-like synoviocytes in rheumatoid ar-thritis: effect of the novel JAK inhibitor peficitinib. Eur. J. Pharmacol. 2020; 882: 173238. https://doi.org/10.1016/j.ejphar.2020.173238
68. Oike T., Sato Y., Kobayashi T., Miyamoto K., Nakamura S., Kaneko Y. et al. Stat3 as a po-tential therapeutic target for rheumatoid arthritis. Sci. Rep. 2017; 7 (1): 10965. https://doi.org/ 10.1038/s41598-017-11233-w
69. Jung J.E., Lee H.G., Cho I.H., Chung D.H., Yoon S-H., Yang Y.M. et al. STAT3is a poten-tial modulator of HIF-1 mediated VEGF expression in human renal carcinoma cells. FASEB J. 2005; 19 (10): 1296-98. https://doi.org/10.1098/fj.04-3099 fje
70. Jung J.E., Kim H.S., Lee C.S., Shin Y.J., Kim Y.N., Kang G.H. et al. STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubuquitination. Exp. Mol. Med. 2008, 40 (5): 479-85. https://doi.org/10.3858/emm.2008.40.5.
71. Qiang L., Wu T., Zhang H-W., Lu N., Hu R., Wang Y-J. et al. HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ. 2012, 19: 284-94. https://doi.org/10.1038/cdd.2011.95
72. Gao W., McCormick J., Connolly M., Balogh E., Veale D.J., Fearon U. Hypoxia and STAT3 signaling interactions regulate pro-inflammatory pathways in rheumatoid arthritis. Ann. Rheum. Dis. 2015; 74 (6): 1275-83. https://doi.org/10.1136/annrheumdis-2013-204105
73. Li G-Q., Zhang Y., Liu D., Qian Y-Y., Zhang H., Guo S-Y. et al. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol. Cell Biochem. 2013; 372: 221-31. https://doi.org/ 10.1007/s1 1010-012-1463-z
74. Slepneva L.V., Khmylova G.A. Failure mechanism of energy metabolism during hypoxia and possible ways to correlation of fumaratecontaining solutions. Transfusiology. 2013; 14 (2): 49-65 (in Russian).
75. Titova O.N., Kuzubova N.A., Lebedeva E.S. The role of the hypoxia signaling pathway in cellular adaptation to hypoxia. RMZH Medicinskoe obozrenie. 2020; 4 (4): 207-13 (in Rus-sian). https://doi.org/10.32364/2587-6821-2020-4-4-207-213
76. Shime H., Yabu M., Akazawa T., Kodama K., Matsumoto M., Seya T. et al. Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J. Immunol. 2008; 180 (11): 7175-83. https://doi.org/10.4049/jimmunol.180.11.7175
77. Haas R., Smith J., Rocher-Ros V., Nadkarni S., Montero-Melendez T., D’Acquisito F. et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol. 2015; 13 (7): e1002202. https://doi.org/ 10.1371/journal.pbio.1002202
78. Yi O., Lin Y., Hu M., Hu S., Su Z., Liao J. et al. Lactate metabolism in rheumatoid arthritis: pathogenic mechanisms and therapeutic intervention with natural compounds. Phytomedicine. 2022; 100: 154048. https://doi.org/10.1016/j.phymed.2022.154048
79. Makino Y., Nakamura H., Ikeda E., Ohnuma K., Yamauchi K., Yabe Y. et al. Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J. Immunol. 2003, 171 (12): 6534-6540. https://doi.org/10.4049/jimmunol.171.12.6534
80. Gaber T., Hȁupl T., Sandig G., Tykwinska K., Fangradt M., Tschirschmann M. et al. Adap-tation of human CD4 T cells to pathophysiological hypoxia: a transcriptome analysis. J. Rheu-matol. 2009; 36 (12): 2655-69. https://doi.org/10.3899/jrheum.090255
81. Lewis J.S., Lee J.A., Underwood J.C., Harris A.L., Lewis C.E. Macrophage responses to hypoxia: relevance to disease mechanisms. J. Leukoc. Biol. 1999; 66 (6): 889-900. https://doi.org/10.1002/jib.66.6.889
82. Cramer T., Yamanishi Y., Clausen B.E., Förster I., Pawlinski R., Mackman N. et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cells. 2003; 112 (5): 645-57. https://doi.org/10.1016/s0092-8674(03)00154-5
83. Blagih J., Jones R.G. Polarizing macrophages through reprogramming of glucose metabolism. Cell. Metab. 2012; 15 (6): 793-95. https://doi.org/10.1016/j.cmet.2012.05.008
84. Riccardi A., Elia A.R., Cappello P., Puppo M., Vanni C., Fardin P. et al. Transcriptome of hypoxic immature dendrite cells: modulation of chemokine/receptor expression. Mol. Cancer Res. 2008; 6 (2): 175-85. https://doi.org/10.1158/1541-7786.MCR-07-0391
85. Yang M., Ma C., Liu S., Sun J., Shao Q., Gao W. et al. Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype and promotes tumour cell migration by dendritic cell-derived osteopontin. Immunology. 2009, 128 (1 Suppl): e237-49. https://doi.org/10.1111/j.1365-2567.2008.02954.x
86. Mancino A., Schioppa T., Larghi P., Pasqualini F., Nebuloni M., Chen I-H. et al. Divergent effects of hypoxia on dendritic cell functions. Blood. 2008, 112 (9): 3723-34. https://doi.org/10.1182/blood-2008-02-142091
87. Blengio F., Raggi F., Pierobon D., Cappello P., Eva A., Giovarelli M. et al. The hypoxic en-vironment reprograms the cytokine/chemokine expression profile of human mature dendritic cells. Immunology. 2013; 218 (1): 76-89. https://doi.org/10.1016/j.imbio.2012.02.002
Published
2024-12-30
How to Cite
Rykunova A. Y., Zverev Y. F. Modern concepts of the pathogenesis of rheumatoid arthritis. // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2024. VOL. 68. № 4. PP. 59–70.
Issue
Section
Reviews
