Skip to main content
SpringerLink
Log in

Critical Role of IL-17 in Experimental Arthritis

  • Chapter
  • First Online:
IL-17, IL-22 and Their Producing Cells: Role in Inflammation and Autoimmunity

Part of the book series: Progress in Inflammation Research ((PIR))

  • 1578 Accesses

Abstract

Since the discovery of IL-17 expression in synovial fluid and biopsies in RA patients, the role of this proinflammatory T cell cytokine in arthritis has been extensively studied using animal models of arthritis. In this chapter, an overview is given of the most important publications elucidating the role of IL-17 in the onset and the progression of experimental arthritis. IL-17 is essential for normal T and B cell development but is also locally involved in the arthritic process, enhancing the expression of proinflammatory cytokines and chemokines. IL-17 also contributes to joint destruction directly by upregulation of MMPs and stimulating osteoclastogenesis through RANKL induction. The recently discovered Th17 cell is regarded as the main source of IL-17, and the influence of IL-12/IL-23 and other mediators in experimental arthritis will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Koenders MI, Kolls JK, Oppers-Walgreen B, van den Bersselaar L, Joosten LA, Schurr JR, Schwarzenberger P, van den Berg WB, Lubberts E (2005) Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis. Arthritis Rheum 52:3239–3247

    Article  PubMed  CAS  Google Scholar 

  2. Nakae S, Nambu A, Sudo K, Iwakura Y (2003) Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 171:6173–6177

    PubMed  CAS  Google Scholar 

  3. Nakae S, Saijo S, Horai R, Sudo K, Mori S, Iwakura Y (2003) IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proc Natl Acad Sci USA 100:5986–5990

    Article  PubMed  CAS  Google Scholar 

  4. Lubberts E, Joosten LA, Oppers B, van den Bersselaar L, Coenen-de Roo CJ, Kolls JK, Schwarzenberger P, van de Loo FA, van den Berg WB (2001) IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 167:1004–1013

    PubMed  CAS  Google Scholar 

  5. Bush KA, Farmer KM, Walker JS, Kirkham BW (2002) Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum 46:802–805

    Article  PubMed  CAS  Google Scholar 

  6. Dudler J, Renggli-Zulliger N, Busso N, Lotz M, So A (2000) Effect of interleukin 17 on proteoglycan degradation in murine knee joints. Ann Rheum Dis 59:529–532

    Article  PubMed  CAS  Google Scholar 

  7. Koenders MI, Lubberts E, van de Loo FA, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Kolls JK, Di Padova FE, Joosten LA, van den Berg WB (2006) Interleukin-17 acts independently of TNF-alpha under arthritic conditions. J Immunol 176:6262–6269

    PubMed  CAS  Google Scholar 

  8. Van Bezooijen RL, van der Wee-Pals L, Papapoulos SE, Löwik CW (2002) Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage destruction in vitro. Ann Rheum Dis 61:870–876

    Article  PubMed  Google Scholar 

  9. Chabaud M, Miossec P (2001) The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 44:1293–1303

    Article  PubMed  CAS  Google Scholar 

  10. Koenders MI, Marijnissen RJ, Devesa I, Lubberts E, Joosten LA, Roth J, van Lent PL, van de Loo FA, van den Berg WB (2011) Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1β, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum 63:2329–2339

    Article  PubMed  CAS  Google Scholar 

  11. Koenders MI, Lubberts E, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Kolls JK, Joosten LA, van den Berg WB (2005) Induction of cartilage damage by overexpression of T cell interleukin-17A in experimental arthritis in mice deficient in interleukin-1. Arthritis Rheum 52:975–983

    Article  PubMed  CAS  Google Scholar 

  12. Lubberts E, van den Bersselaar L, Oppers-Walgreen B, Schwarzenberger P, Coenen-de Roo CJ, Kolls JK, Joosten LA, van den Berg WB (2003) IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. J Immunol 170:2655–2662

    PubMed  CAS  Google Scholar 

  13. Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50:650–659

    Article  PubMed  CAS  Google Scholar 

  14. Koenders MI, Devesa I, Marijnissen RJ, Abdollahi-Roodsaz S, Boots AM, Walgreen B, di Padova FE, Nicklin MJ, Joosten LA, van den Berg WB (2008) Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice. Arthritis Rheum 58:3461–3470

    Article  PubMed  CAS  Google Scholar 

  15. Koenders MI, Lubberts E, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Di Padova FE, Boots AM, Gram H, Joosten LA, van den Berg WB (2005) Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol 167:141–149

    Article  PubMed  CAS  Google Scholar 

  16. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914

    Article  PubMed  CAS  Google Scholar 

  17. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (2003) Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198:1951–1957

    Article  PubMed  CAS  Google Scholar 

  18. Cho ML, Kang JW, Moon YM, Nam HJ, Jhun JY, Heo SB, Jin HT, Min SY, Ju JH, Park KS et al (2006) STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol 176:5652–5661

    PubMed  CAS  Google Scholar 

  19. Guedez YB, Whittington KB, Clayton JL, Joosten LA, van de Loo FA, van den Berg WB, Rosloniec EF (2001) Genetic ablation of interferon-gamma up-regulates interleukin-1beta expression and enables the elicitation of collagen-induced arthritis in a non-susceptible mouse strain. Arthritis Rheum 44:2413–2424

    Article  PubMed  CAS  Google Scholar 

  20. Chu CQ, Swart D, Alcorn D, Tocker J, Elkon KB (2007) Interferon-gamma regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17. Arthritis Rheum 56:1145–1151

    Article  PubMed  CAS  Google Scholar 

  21. Irmler IM, Gajda M, Bräuer R (2007) Exacerbation of antigen-induced arthritis in IFN-gamma-deficient mice as a result of unrestricted IL-17 response. J Immunol 179:6228–6236

    PubMed  CAS  Google Scholar 

  22. Glant TT, Finnegan A, Mikecz K (2003) Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics. Crit Rev Immunol 23:199–250

    Article  PubMed  CAS  Google Scholar 

  23. Lubberts E, Joosten LA, Chabaud M, van Den Bersselaar L, Oppers B, Coenen-De Roo CJ, Richards CD, Miossec P, van Den Berg WB (2000) IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion. J Clin Invest 105:1697–1710

    Article  PubMed  CAS  Google Scholar 

  24. Sarkar S, Tesmer LA, Hindnavis V, Endres JL, Fox DA (2007) Interleukin-17 as a molecular target in immune-mediated arthritis: immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin-4. Arthritis Rheum 56:89–100

    Article  PubMed  CAS  Google Scholar 

  25. Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S (2007) T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med 204:41–47

    Article  PubMed  CAS  Google Scholar 

  26. Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP (2006) Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum 54:158–168

    Article  PubMed  CAS  Google Scholar 

  27. Ruchatz H, Leung BP, Wei XQ, McInnes IB, Liew FY (1998) Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology. J Immunol 160:5654–5660

    PubMed  CAS  Google Scholar 

  28. Ferrari-Lacraz S, Zanelli E, Neuberg M, Donskoy E, Kim YS, Zheng XX, Hancock WW, Maslinski W, Li XC, Strom TB, Moll T (2004) Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis. J Immunol 173:5818–5826

    PubMed  CAS  Google Scholar 

  29. Yoshihara K, Yamada H, Hori A, Yajima T, Kubo C, Yoshikai Y (2007) IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17. Eur J Immunol 37:2744–2752

    Article  PubMed  CAS  Google Scholar 

  30. Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, Senices M, Wu PW, Sibley B, Leathurby Y, Brown TP, Nickerson-Nutter C, Keith JC Jr, Collins M (2007) Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum 56:1152–1163

    Article  PubMed  CAS  Google Scholar 

  31. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448:480–483

    Article  PubMed  CAS  Google Scholar 

  32. Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, Oukka M, Kuchroo VK (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448:484–487

    Article  PubMed  CAS  Google Scholar 

  33. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454:350–352

    Article  PubMed  CAS  Google Scholar 

  34. Marijnissen RJ, Koenders MI, Smeets RL, Stappers MH, Nickerson-Nutter C, Joosten LA, Boots AM, van den Berg WB (2011) Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation. Arthritis Rheum 63:2939–2948

    Article  PubMed  CAS  Google Scholar 

  35. Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, Senices M, Gill D, Dunussi-Joannopoulos K, Collins M, Nickerson-Nutter C, Fouser LA, Young DA (2008) IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118:597–607

    PubMed  CAS  Google Scholar 

  36. Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B (2007) IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 179:8098–8104

    PubMed  CAS  Google Scholar 

  37. Goldberg R, Wildbaum G, Zohar Y, Maor G, Karin N (2004) Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J Immunol 173:1171–1178

    PubMed  CAS  Google Scholar 

  38. Cao Y, Doodes PD, Glant TT, Finnegan A (2008) IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol 180:922–930

    PubMed  CAS  Google Scholar 

  39. Abdollahi-Roodsaz S, Joosten LA, Koenders MI, Devesa I, Roelofs MF, Radstake TR, Heuvelmans-Jacobs M, Akira S, Nicklin MJ, Ribeiro-Dias F, van den Berg WB (2008) Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest 118:205–216

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, 9101, 6500 HB, Nijmegen, The Netherlands

    Marije I. Koenders & Wim B. van den Berg

Authors
  1. Marije I. Koenders
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wim B. van den Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wim B. van den Berg .

Editor information

Editors and Affiliations

  1. Institut de Transgénose, Labo. d'Immunologie et, CNRS, rue de la Férollerie 3B, Orleans CX 2, 45071, France

    Valérie Quesniaux

  2. Institut de Transgénose, Labo. d'Immunologie et, CNRS, rue de la Férollerie 3B, Orleans CX 2, 45071, France

    Bernhard Ryffel

  3. Novartis Institute for Biomedical, Research (NIBR), Novartis Pharma AG, Basel, 4002, Switzerland

    Franco Padova

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Basel

About this chapter

Cite this chapter

Koenders, M.I., van den Berg, W.B. (2013). Critical Role of IL-17 in Experimental Arthritis. In: Quesniaux, V., Ryffel, B., Padova, F. (eds) IL-17, IL-22 and Their Producing Cells: Role in Inflammation and Autoimmunity. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0522-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-0522-3_9

  • Published:

  • Publisher Name: Springer, Basel

  • Print ISBN: 978-3-0348-0521-6

  • Online ISBN: 978-3-0348-0522-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation