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Научно-практическая ревматология

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Роль Toll-подобных рецепторов и их эндогенных лигандов в патогенезе ревматоидного артрита (обзор литературы)

https://doi.org/10.14412/1995-4484-2016-78-85

Аннотация

Несмотря на большие достижения в изучении патогенеза ревматоидного артрита (РА), позволившие создать принципиально новый класс фундаментально обоснованных терапевтических агентов, многие иммунологические аспекты остаются не до конца изученными. Одним из важных вопросов патогенеза не только РА, но и всех ревматических заболеваний является роль механизмов врожденного иммунитета в развитии аутоиммунного воспаления. Открытие паттерн-распознающих рецепторов (ПРР) позволило фундаментальной иммунологии сделать большой шаг вперед в понимании того, каким образом реализуются данные механизмы. Изучение мембранных и эндосомальных Toll-подобных рецепторов (ТПР) – наиболее обширной и хорошо изученной группы ПРР – является перспективным направлением современной ревматологии. Важно отметить, что стимулировать ТПР способны некоторые молекулярные агенты, присутствие которых в ткани ассоциировано с ее повреждением. Они получили название молекулярных паттернов, ассоциированных с повреждением (МПАП). В статье представлен обзор литературы, посвященной механизмам реализации ТПР-опосредованных сигнальных путей, различным аспектам роли отдельных ТПР и МПАП в индукции и поддержании аутоиммунного воспаления при РА, а также перспективам таргетной терапии, направленной на ингибирование некоторых ТПР и МПАП.

Об авторе

М. Ю. Волков
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой
Россия
Москва, 115522 Москва, Каширское шоссе, 34А


Список литературы

1. Rock F. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci. 1998;95:588-93. doi: 10.1073/pnas.95.2.588

2. Лебедев КА, Понякина ИД. Иммунология образраспознающих рецепторов: Интегральная иммунология. 2-е изд. Москва: Книжный дом «ЛИБРОКОМ»; 2013. 256 с. [Lebedev KA, Ponyakina ID. Immunologiya obrazraspoznayushchikh retseptorov: Integral’naya immunologiya [Immunology of image recognition receptors: Integrated Immunology]. 2nd ed. Moscow: Knizhnyi dom «LIBROKOM»; 2013. 256 p.].

3. Chen JQ, Szodoray P, Zeher M. Toll-like receptor pathways in autoimmune diseases. Clin Rev Allergy Immunol. 2015 Feb 17. [Epub ahead of print].

4. Cao Z, Henzel WJ, Gao X. IRAK: a kinase associated with the interleukin-1 receptor. Science. 1996;271:1128-31. doi: 10.1126/science.271.5252.1128

5. Mansell A, Smith R, Doyle SL, et al. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol. 2006;7:148-55. doi: 10.1038/ni1299

6. Goh FG, Midwood KS. Intrinsic danger: activation of Toll-like receptors inrheumatoid arthritis. Rheumatology (Oxford). 2012;51(1):7-23. doi: 10.1093/rheumatology/ker257

7. Rogier R, Koenders MI, Abdollahi-Roodsaz S. Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis. J Immunol Res. 2015;2015:527696. doi: 10.1155/2015/527696

8. Coenen MJH, Enevold C, Barrera P, et al. Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome. PLoS One. 2010;5:e14326. doi: 10.1371/journal.pone.0014326

9. Jaen O, Petit-Teixeira E, Kirsten H, et al. No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis. Arthritis Res Ther. 2009; 11:R5. doi: 10.1186/ar2589

10. Etem EO, Elyas H, Ozgocmen S, et al. The investigation of tolllike receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients. Rheumatol Int. 2011;31:1369-74. doi: 10.1007/s00296-010-1472-8

11. Enevold C, Radstake TRD, Coenen MJH, et al. Multiplex screening of 22 single-nucleotide polymorphisms in 7 Toll-like receptors: an association study in rheumatoid arthritis. J Rheumatol. 2010;37:905-10. doi: 10.3899/jrheum.090775

12. Davis ML, LeVan TD, Yu F, et al. Associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression: an observational cohort study. Int Immunopharmacol. 2015;24(2):346-52. doi: 10.1016/j.intimp.2014.12.030

13. Sacre SM, Andreakos E, Kiriakidis S, et al. The Toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritis. Am J Pathol. 2007;170:518-25. doi: 10.2353/ajpath.2007.060657

14. Brentano F, Schorr O, Gay RE, et al. RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum. 2005;52:2656-65. doi: 10.1002/art.21273

15. Sacre SM, Lo A, Gregory B, et al. Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. J Immunol. 2008;181:8002-9. doi: 10.4049/jimmunol.181.11.8002

16. Ospelt C, Brentano F, Rengel Y, et al. Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis. Arthritis Rheum. 2008;58:3684-92. doi: 10.1002/art.24140

17. Roelofs MF, Wenink MH, Brentano F, et al. Type I interferons might form the link between Toll-like receptor (TLR) 3/7 and TLR4-mediated synovial inflammation in rheumatoid arthritis (RA). Ann Rheum Dis. 2009;68:1486-93. doi: 10.1136/ard.2007.086421

18. Tamaki Y, Takakubo Y, Hirayama T, et al. Expression of Toll-like receptors and their signaling pathways in rheumatoid synovitis. J Rheumatol. 2011;38:810-20. doi: 10.3899/jrheum.100732

19. Radstake TRDJ, Roelofs MF, Jenniskens YM, et al. Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum. 2004;50:3856-65. doi: 10.1002/art.20678

20. Seibl R, Birchler T, Loeliger S, et al. Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. Am J Pathol. 2003;162:1221-7. doi: 10.1016/S0002-9440(10)63918-1

21. Pierer M, Rethage J, Seibl R, et al Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol. 2004;172:1256-65. doi: 10.4049/jimmunol.172.2.1256

22. McGarry T, Veale DJ, Gao W, et al. Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthritis. Arthritis Res Ther. 2015 Jun 9;17:153. doi: 10.1186/s13075-015-0664-8.

23. Chen Z, Su L, Xu Q, et al. IL-1R/TLR2 through MyD88 divergently modulates osteoclastogenesis through regulation of nuclear factor of activated T cells c1 (NFATc1) and B lymphocyte-induced maturation protein-1 (Blimp1). J Biol Chem. 2015 Oct 19. pii: jbc.M115.663518. [Epub ahead of print]. doi: 10.1074/jbc.m115.663518

24. Hu F, Li Y, Zheng L, et al. Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and th17 cell responses in rheumatoid arthritis. PLoS One. 2014 Jun 17;9(6):e100266. doi: 10.1371/journal.pone.0100266

25. Roelofs MF, Joosten LA, Abdollahi-Roodsaz S, et al. The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum. 2005;52:2313-22. doi: 10.1002/art.21278

26. Caiello I, Minnone G, Holzinger D, et al. IL-6 amplifies _LR mediated cytokine and chemokine production: implications for thepathogenesis of rheumatic inflammatory diseases. PLoS One. 2014;9(10):e107886.

27. Kim K-W, Cho M-L, Oh H-J, et al. ТLR-3 enhances osteoclastogenesis through upregulation of RANKL expression from fibroblast-like synoviocytes in patients with rheumatoid arthritis. Immunol Lett. 2009;124:9-17. doi: 10.1016/j.imlet.2009.02.006

28. Kinnebrew MA, Buffie CG, Diehl GE, et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity. 2012 Feb 24;36(2):276-87. doi: 10.1016/j.immuni.2011.12.011

29. Komai-Koma M, Li D, Wang E, et al. Anti-Toll-like receptor 2 and 4 antibodies suppress inflammatory response in mice. Immunology. 2014;143(3):354-62. doi: 10.1111/imm.12312

30. Meng L, Zhu W, Jiang C, et al. Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats. Arthritis Res Ther. 2010;12(3):R103. doi: 10.1186/ar3034

31. Zhu W, Meng L, Jiang C, et al. Overexpression of toll-like receptor 3 in spleen is associated with experimental arthritis in rats. Scand J Immunol. 2012 Sep;76(3):263-70. doi: 10.1111/j.1365-3083.2012.02724.x

32. Yarilina A, DiCarlo E, Ivashkiv LB. Suppression of the effector phase of inflammatory arthritis by double-stranded RNA is mediated by type I IFNs. J Immunol. 2007;178(4):2204-11. doi: 10.4049/jimmunol.178.4.2204

33. Hayashi T, Gray CS, Chan M, et al. Prevention of autoimmune disease by induction of tolerance to Toll-like receptor 7. Proc Natl Acad Sci U S A. 2009;106(8):2764-69. doi: 10.1073/pnas.0813037106

34. Alzabin S, Kong P, Medghalchi M, et al. Investigation of the role of endosomal Toll-like receptors in murine collagen-induced arthritis reveals a potential role for ТLR7 in disease maintenance. Arthritis Res Ther. 2012;14(3):R142.

35. Chen SY, Shiau AL, Li YT, et al. Suppression of collagen-induced arthritis by intra-articular lentiviral vector-mediated delivery of Toll-like receptor 7 short hairpin RNA gene. Gene Ther. 2012;19(7):752-60. doi: 10.1038/gt.2011.173

36. Demaria O, Pagni PP, Traub S, et al. ТLR8 deficiency leads to autoimmunity in mice. J Clin Invest. 2010;120(10):3651-62.

37. Miles K, Heaney J, Sibinska Z, et al. A tolerogenic role for Tolllike receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells. Proc Natl Acad Sci U S A. 2012;109(3):887-92. doi: 10.1073/pnas.1109173109

38. Begovich AB, Carlton VE, Honigberg LA, et al. A missense singlenucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004;75(2):330-7. doi: 10.1086/422827

39. Wang Y, Stanford S, Zhou W, et al. Rheumatoid arthritis-associated PTPN22 modulates toll-like receptor-mediated, type 1 interferon-dependent innate immunoregulation [abstract]. Arthritis Rheum. 2012;64(Suppl 10):2452.

40. Herman S, Fischer A, Pfatschbacher J, et al. A ТLR 9 antagonist diminishes arthritis severity in a rat model of rheumatoid arthritis. Ann Rheum Dis. 2011;70(Suppl 2):A39.

41. Isomä ki P, Alanä rä T, Isohanni P, et al. The expression of SOCS is altered in rheumatoid arthritis. Rheumatol Oxf Engl. 2007;46:1538-46. doi: 10.1093/rheumatology/kem198

42. Tsao J-T, Kuo C-C, Lin S-C. The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Clin Exp Med. 2008;8:179-85. doi: 10.1007/s10238-008-0006-0

43. Sanjuan MA, Rao N, Lai KT, et al. CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion. J Cell Biol. 2006;172(7):1057-68. doi: 10.1083/jcb.200508058

44. Kuznik A, Bencina M, Svajger U, et al. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol. 2011;186(8):4794-804. doi: 10.4049/jimmunol.1000702

45. Thwaites R, Chamberlain G, Sacre S. Emerging role of endosomal Toll-like receptors in rheumatoid arthritis. Frontiers in Immunology. 2014;5:1. doi: 10.3389/fimmu.2014.00001

46. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418:191-5. doi: 10.1038/nature00858

47. Andersson U, Wang H, Palmblad K, et al. High mobility group 1 protein (Hmgb-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192:565-70. doi: 10.1084/jem.192.4.565

48. Schierbeck H, Lundback P, Palmblad K, et al. Monoclonal antiHMGB1 (high mobility group box chromosomal protein 1) antibody protection in two experimental arthritis models. Mol Med. 2011;17:1039-44. doi: 10.2119/molmed.2010.00264

49. Hamada T, Torikai M, Kuwazuru A, et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum. 2008;58:2675-85. doi: 10.1002/art.23729

50. Foell D, Kane D, Bresnihan B, et al. Expression of the proinflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis. Rheumatology. 2003;42:1383-9. doi: 10.1093/rheumatology/keg385

51. Madland TM, Larsen A, Brun JG. S100 proteins calprotectin and S100A12 are related to radiographic changes rather than disease activity in psoriatic arthritis with low disease activity. J Rheumatol. 2007;34:2089-92.

52. Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425:516-21. doi: 10.1038/nature01991

53. Liu-Bryan R, Scott P, Sydlaske A, et al. Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005;52:2936-46. doi: 10.1002/art.21238

54. Campo GM, Avenoso A, D'Ascola A, et al. The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis. J Cell Biochem. 2012;113:1852-67. doi: 10.1002/jcb.24054

55. Horton MR, Burdick MD, Strieter RM, et al. Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-γ in mouse macrophages. J Immunol. 1998;160:3023-30.

56. Midwood K, Sacre S, Piccinini AM, et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med. 2009;15:774-80. doi: 10.1038/nm.1987

57. Goh FG, Piccinini AM, Krausgruber T, et al. Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation. J Immunol. 2010;184:2655-62. doi: 10.4049/jimmunol.0903359

58. Zhao X, Okeke N, Sharpe O, et al. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis. Arthritis Res Ther. 2008;10:R94. doi: 10.1186/ar2478

59. Sokolove J, Zhao X, Chandra PE, Robinson WH. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum. 2011;63:53-62. doi: 10.1002/art.30081

60. Sanchez-Pernaute O, Filkova M, Gabucio A, et al. Citrullination enhances the pro-inflammatory response to fibrin in rheumatoid arthritis synovial fibroblasts. Ann Rheum Dis. 2013;72:1400-6. doi: 10.1136/annrheumdis-2012-201906

61. Cordova KN, Willis VC, Haskins K, Holers VM. A citrullinated fibrinogen-specific T cell line enhances autoimmune arthritis in a mouse model of rheumatoid arthritis. J Immunol. 2013;190:1457-65. doi: 10.4049/jimmunol.1201517

62. Wendling U, Paul L, van der Zee R, et al. A conserved mycobacterial heat shock protein (hsp) 70 sequence prevents adjuvant arthritis upon nasal administration and induces IL-10-producing T cells that cross-react with the mammalian self-hsp70 homologue. J Immunol. 2000;164:2711-7. doi: 10.4049/jimmunol.164.5.2711

63. Wieten L, Berlo SE, ten Brink CB, et al. IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis. PLoS One. 2009;4:e4186. doi: 10.1371/journal.pone.0004186

64. O'Reilly S. Pound the alarm: danger signals in rheumatic diseases. Clin Sci (Lond). 2015;128(5):297-305. doi: 10.1042/CS20140467

65. Mullen L, Chamberlain G, Sacre S. Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease. Arthritis Res Ther. 2015;17:122. doi: 10.1186/s13075-015-0645-y

66. Idera Clinical Programs: Overview (2015) [цит. от 12.01.16]. Available from: http://www.iderapharma.com/

67. Musumeci D., Roviello GN, Montesarchio D. An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharm Ther. 2013;141(3):347-57. doi: 10.1016/j.pharmthera.2013.11.001


Рецензия

Для цитирования:


Волков М.Ю. Роль Toll-подобных рецепторов и их эндогенных лигандов в патогенезе ревматоидного артрита (обзор литературы). Научно-практическая ревматология. 2016;54(1):78-85. https://doi.org/10.14412/1995-4484-2016-78-85

For citation:


Volkov M.Yu. ROLE OF TOLL-LIKE RECEPTORS AND THEIR ENDOGENOUS LIGANDS IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS: A REVIEW OF LITERATURE. Rheumatology Science and Practice. 2016;54(1):78-85. (In Russ.) https://doi.org/10.14412/1995-4484-2016-78-85

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ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)