Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Requirement of IL-17 receptor signaling in resident synoviocytes for development of full blown destructive arthritis

  • E Lubberts1, 2,
  • P Schwarzenberger2,
  • W Huang2,
  • JR Schurr2,
  • JJ Peschon3,
  • WB van den Berg1 and
  • JK Kolls2
Arthritis Research & Therapy20057(Suppl 1):P112

DOI: 10.1186/ar1633

Received: 11 January 2005

Published: 17 February 2005

Chronic arthritis is characterized by persistent joint inflammation and concomitant joint destruction. IL-17 is a novel proinflammatory T-cell cytokine suspected to be involved in inflammatory and autoimmune diseases such as rheumatoid arthritis. Here, we report that IL-17 receptor (IL-17R) signaling is required in resident synovial cells for full progression of chronic synovitis and bone erosion. Repeated injections of Gram-positive bacterial cell wall fragments (SCW) directly into the knee joint of naïve IL-17R-deficient (IL-17R-/-) mice had no effect on the acute phase of arthritis but prevented progression to chronic destructive synovitis as was noted in wild-type (wt) mice. Micro-array analysis revealed significant down-regulation of leukocyte-specific chemokines, selectins, collagenase-3, and IL-1 in the synovium of IL-17R-/- mice. Bone marrow (BM) chimeric mice revealed the need for IL-17/IL-17R signaling in resident synovial cells for development of full blown synovitis. Chimeric mice of host wt and donor IL-17R-/- BM cells developed destructive synovitis in this chronic relapsing SCW arthritis model similar to wt → wt chimeras. In contrast, chimeric mice of host IL-17R-/- and donor wt BM cells were protected from full blown destructive arthritis similar to IL-17R-/- → IL-17R-/- chimeras. These data strongly suggest T-cell IL-17-IL-17R signaling in resident synovial cells to be a pivotal mechanism through which an acute macrophage-driven joint inflammation progresses into a chronic destructive synovitis. Prevention of local synovial IL-17-IL-17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis.

Authors’ Affiliations

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

Copyright

© BioMed Central Ltd 2005

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