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


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

LSU Health Sciences Center, Department of Medicine, Gene Therapy Program
University Medical Center St Radboud, Department of Rheumatology, Rheumatology and Advanced Therapeutics


© BioMed Central Ltd 2004