The interleukin-23/interleukin-17 axis in spondyloarthritis

Current Opinion in Rheumatology

Volumn 20, Issue 4, 2008, Pages 392-397

  Layh Schmitt, Gerlinde ^a   Colbert, Robert A ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

Ankylosing spondylitis; Cytokines; Inflammation; Spondyloarthritis; T cells

Indexed keywords

GAMMA INTERFERON; HLA B27 ANTIGEN; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 23 RECEPTOR; INTERLEUKIN 6; TRANSFORMING GROWTH FACTOR BETA; CYTOKINE; IL23R PROTEIN, HUMAN; INTERLEUKIN RECEPTOR;

AUTOIMMUNE DISEASE; CD4+ T LYMPHOCYTE; CYTOKINE PRODUCTION; DISEASE COURSE; DNA POLYMORPHISM; HUMAN; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SPONDYLOARTHROPATHY; TH1 CELL; TH2 CELL; GENETIC POLYMORPHISM; GENETICS; IMMUNOLOGY;

CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; HLA-B27 ANTIGEN; HUMANS; INTERLEUKIN-17; INTERLEUKIN-23; POLYMORPHISM, GENETIC; RECEPTORS, INTERLEUKIN; SPONDYLARTHROPATHIES;

EID: 47049123836     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/BOR.0b013e328303204b     Document Type: Review

References (75)

1. Acosta-Rodriguez EV, Rivino L, Geginat J, et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 2007; 8:639-646. Human Th17 T cells.
2. Happel KI, Dubin PJ, Zheng M, et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med 2005; 202:761-769.
3. LeibundGut-Landmann S, Gross O, Robinson MJ, et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 2007; 8:630-638.
4. Rudner XL, Happel KI, Young EA, Shellito JE. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect Immun 2007; 75:3055-3061.
5. Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 2006; 116:1310-1316.
6. Uhlig HH, McKenzie BS, Hue S, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 2006; 25:309-318.
7. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201:233-240.
8. Chen Y, Langrish CL, McKenzie B, et al. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 2006; 116:1317-1326.
9. Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007; 445:648-651. Th17 cytokines in the pathogenesis of skin inflammation.
10. Yao Z, Painter SL, Fanslow WC, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol 1995; 155:5483-5486.
11. Yao Z, Fanslow WC, Seldin MF, et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 1995; 3:811-821.
12. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6:1123-1132.
13. Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005; 6:1133-1141.
14. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 2007; 25:821-852. Comprehensive review article.
15. Langrish CL, McKenzie BS, Wilson NJ, et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 2004; 202:96-105.
16. Mangan PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006; 441:231-234.
17. McGeachy MJ, Bak-Jensen KS, Chen Y, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 2007; 8:1390-1397.
18. Sutton C, Brereton C, Keogh B, et al. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 2006; 203:1685-1691.
19. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor ROR-gammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126:1121-1133.
20. Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 2008; 28:29-39.
21. Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003; 278:1910-1914.
22. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 2007; 25:221-242. Comprehensive review of regulatory networks.
23. Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007; 8:950-957. Points out important features of human Th17 T cells.
24. Hoeve MA, Savage ND, de Boer T, et al. Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol 2006; 36:661-670.
25. Amadi-Obi A, Yu CR, Liu X, et al. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 2007; 13:711-718.
26. Chu CQ, Swart D, Alcorn D, et al. Interferon-gamma regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17. Arthritis Rheum 2007; 56:1145-1151. Provides evidence that IFN-γ inhibits pathogenic Th17 T cells.
27. Laurence A, Tato CM, Davidson TS, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 2007; 26:371-381.
28. Stumhofer JS, Laurence A, Wilson EH, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 2006; 7:937-945.
29. Batten M, Li J, Yi S, et al. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 2006; 7:929-936.
30. Fitzgerald DC, Zhang GX, El-Behi M, et al. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 2007; 8:1372-1379.
31. Awasthi A, Carrier Y, Peron JP, et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 2007; 8:1380-1389.
32. Stumhofer JS, Silver JS, Laurence A, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 2007; 8:1363-1371.
33. Mucida D, Park Y, Kim G, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007; 317:256-260. Possible regulatory role of retinoic acid in Th17 and Treg function.
34. Elias KM, Laurence A, Davidson TS, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008; 111:1013-1020. Evidence for retinoic acid controlling Th17 polarization.
35. Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003; 421:744-748.
36. Liang SC, Tan XY, Luxenberg DP, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203:2271-2279.
37. Ma HL, Liang S, Li J, et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 2008; 118:597-607. The importance of other Th17 cytokines in mediating pathogenic processes.
38. Chen Z, Tato CM, Muul L, et al. Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 2007; 56:2936-2946. Information on human Th17 regulation.
39. Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells. J Exp Med 2007; 204:1849-1861. Information on human Th17 regulation.
40. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 2003; 171: 6173-6177.
41. Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003; 198:1951-1957.
42. Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13:715-725.
43. Lock C, Hermans G, Pedotti R, et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002; 8:500-508.
44. Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52:65-70.
45. Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999; 103:1345-1352.
46. Matusevicius D, Kivisakk P, He B, et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 1999; 5:101-104.
47. Nielsen OH, Kirman I, Rudiger N, et al. Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand J Gastroenterol 2003; 38:180-185.
48. Honorati MC, Meliconi R, Pulsatelli L, et al. High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients. Rheumatology (Oxford) 2001; 40:522-527.
49. Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 2006; 203:2673-2682.
50. Dong C. Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat Rev Immunol 2006; 6:329-333.
51. Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314:1461-1463.
52. Dubinsky MC, Wang D, Picornell Y, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis 2007; 13:511-515. IL23R gene polymorphisms and susceptibility to disease.
53. Oliver J, Rueda B, Lopez-Nevot MA, et al. Replication of an association between IL23R gene polymorphism with inflammatory bowel disease. Clin Gastroenterol Hepatol 2007; 5:977-981. IL23R gene polymorphisms and susceptibility to disease.
54. Duerr RH. Genome-wide association studies herald a new era of rapid discoveries in inflammatory bowel disease research. Gastroenterology 2007; 132:2045-2049.
55. Baldassano RN, Bradfield JP, Monos DS, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol 2007; 5:972-976.
56. Borgiani P, Perricone C, Ciccacci C, et al. Interleukin-23R Arg381Gln is associated with susceptibility to Crohn's disease but not with phenotype in an Italian population. Gastroenterology 2007; 133:1049-1051; author reply 1051-1042.
57. Tremelling M, Cummings F, Fisher SA, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology 2007; 132:1657-1664.
58. Cummings JR, Ahmad T, Geremia A, et al. Contribution of the novel inflammatory bowel disease gene IL23R to disease susceptibility and phenotype. Inflamm Bowel Dis 2007; 13:1063-1068. IL23R gene polymorphisms and susceptibility to disease.
59. Buning C, Schmidt HH, Molnar T, et al. Heterozygosity for IL23R p.Arg381Gln confers a protective effect not only against Crohn's disease but also ulcerative colitis. Aliment Pharmacol Ther 2007; 26:1025-1033.
60. Cargill M, Schrodi SJ, Chang M, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007; 80:273-290. IL23R gene polymorphisms and susceptibility to disease.
61. Tsunemi Y, Saeki H, Nakamura K, et al. Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatol Sci 2002; 30:161-166.
62. Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008; 58:15-25.
63. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine 2007; 74:304-305. A small study showing IL-17 elevations in patients with AS.
64. Singh R, Aggarwal A, Misra R. Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol 2007; 34:2285-2290. Evidence for elevated IL-17 in SpA.
65. Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol 2008; 35:515-519.
66. Rudwaleit M, Siegert S, Yin Z, et al. Low T cell production of TNFα and IFN γ in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism. Ann Rheum Dis 2001; 60:36-42.
67. Bas S, Kvien TK, Buchs N, et al. Lower level of synovial fluid interferon-gamma in HLA-B27-positive than in HLA-B27-negative patients with Chlamydia trachomatis reactive arthritis. Rheumatology (Oxford) 2003; 42:461-467.
68. Smith JA, Barnes MG, Hong D, et al. Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals IFN-γ dysregulation. Arthritis Rheum 2008; 58 (in press). This paper provides evidence for low IFN-γ expression in macrophages from patients with AS as a possible primary defect.
69. Inman RD, Chiu B. Early cytokine profiles in the joint define pathogen clearance and severity of arthritis in Chlamydia-induced arthritis in rats. Arthritis Rheum 2006; 54:499-507.
70. Turner MJ, Delay ML, Bai S, et al. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: Implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheum 2007; 56:215-223. Demonstrates importance of regulation of HLA-B27 expression in UPR activation.
71. Smith JA, Turner MJ, DeLay ML, et al. Endoplasmic reticulum stress and the unfolded protein response are linked to synergistic IFN-β upregulation via XBP-1. Eur J Immunol 2008; 38 (in press). Links endoplasmic reticulum stress caused by protein (including HLA-B27) misfolding to cytokine dysregulation.
72. Colbert RA, Turner MJ, DeLay ML, et al. HLA-B27 misfolding activates the IL-23/IL-17 axis via the unfolded protein response in transgenic rats: evidence for a novel mechanism of inflammation. Arthritis Rheum 2007; 54:S515.
73. Burton PR, Clayton DG, Cardon LR, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 2007; 39:1329-1337. Whole genome association study identifying two new genes involved in AS susceptibility.
74. Rueda B, Orozco G, Raya E, et al. The IL23R Arg381Gln nonsynonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann Rheum Dis 2008 (in press). Confirms IL23R SNP in susceptibility to AS.
75. Colbert RA. HLA-B27 misfolding and spondyloarthropathies. In: Lopez-Larrea C. editor. Molecular mechanisms of spondyloarthropathies. Austin, Texas: Landes Bioscience/Eurekah; 2008 (in press).