Volume 6 Supplement 1

24th European Workshop for Rheumatology Research

Open Access

Requirement of local synovial IL-17 receptor signaling in the progression of chronic synovitis and bone erosion in arthritis

  • E Lubberts1, 2,
  • W Huang1,
  • P Schwarzenberger1,
  • J Schurr1,
  • J Peschon3,
  • WB van den Berg2 and
  • JK Kolls1
Arthritis Res Ther20046(Suppl 1):58

https://doi.org/10.1186/ar1100

Received: 16 January 2004

Published: 24 February 2004

IL-17 is a proinflammatory cytokine that is suspected to be involved in development of rheumatoid arthritis (RA). However, the role of IL-17–IL-17 receptor signaling in the effector phase of arthritis, including requirement of this signaling pathway in synoviocytes, is still not fully elucidated. Here we demonstrate, using IL-17 receptor deficient (IL-17R-/-) mice, a requirement for IL-17R signaling in immune reactivity and progression of synovitis and bone erosion in a T cell mediated mBSA arthritis model and chronic streptococcal cell wall arthritis. Of great interest, chimeric mice of host wild-type (wt) and donor IL-17R-/- bone marrow (BM) cells developed chronic synovitis similar to that in wt/wt chimeras. In contrast, chimeric mice of host IL-17R-/- and donor wt BM cells were protected from progressive synovitis similar to IL-17R-/-/ IL-17R-/- chimeras, suggesting a crucial role of resident synovial cells. Weakened mobilization of neutrophils into the joint and downregulation of synovial mRNA expression for leukocyte specific chemokines and selectins, and MMP-1 was found in IL-17R-/- mice. These data suggest that, in addition to the role played by IL-17–IL-17R signaling in development of immunity, synovial IL-17–IL-17R signaling plays a critical role in the effector phase of arthritis. Activation of IL-17R on fibroblast-like synoviocytes appears pivotal.

Authors’ Affiliations

(1)
LSU Health Sciences Center, Department of Medicine, Gene Therapy Program
(2)
University Medical Center St Radboud, Department of Rheumatology, Rheumatology and Advanced Therapeutics
(3)
Amgen

Copyright

© BioMed Central Ltd 2004

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