Ms Willis owns stock or stock options in Amgen Inc.
Rheumatoid Arthritis Basic Science Studies
Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7–induced immune activation in rheumatoid arthritis
Article first published online: 27 AUG 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 9, pages 2595–2605, September 2009
How to Cite
Hartgring, S. A. Y., van Roon, J. A. G., Wijk, M. W.-v., Jacobs, K. M. G., Jahangier, Z. N., Willis, C. R., Bijlsma, J. W. J. and Lafeber, F. P. J. G. (2009), Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7–induced immune activation in rheumatoid arthritis. Arthritis & Rheumatism, 60: 2595–2605. doi: 10.1002/art.24754
- Issue published online: 27 AUG 2009
- Article first published online: 27 AUG 2009
- Manuscript Accepted: 17 MAY 2009
- Manuscript Received: 19 JUN 2008
- Dutch Arthritis Association
To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7Rα) in patients with rheumatoid arthritis (RA).
Expression of IL-7Rα and IL-7 was determined in synovial tissue from RA patients and was compared with that in synovial tissue from patients with undifferentiated arthritis (UA) and osteoarthritis (OA). IL-7Rα expression on CD4 T cells, CD19 B cells, and CD14 monocyte/macrophages from RA synovial tissue, synovial fluid, and peripheral blood was also assessed. The proliferative capacity of IL-7Rαbright and IL-7Rαdim/− T cells was measured. In addition, we examined IL-7R blockade with soluble human IL-7Rα (hIL-7Rα) in the prevention of immune activation of peripheral blood mononuclear cells.
We found significantly higher IL-7Rα expression in RA and UA synovial tissue than in OA synovial tissue, and the level of IL-7Rα expression correlated significantly with the levels of CD3 and IL-7 expression. CD4 T cells from RA synovial fluid and synovial tissue strongly expressed IL-7Rα. A substantial percentage of B cells and macrophages from RA synovial fluid and synovial tissue also expressed IL-7Rα, although less prominently than T cells. We found that peripheral blood IL-7Rαbright T cells that did not express FoxP3 were highly proliferative as compared with IL-7Rαdim/− T cells that did express high levels of FoxP3. Soluble hIL-7Rα inhibited IL-7–induced proliferation and interferon-γ production by mononuclear cells from RA patients.
Our data suggest that enhanced expression of IL-7Rα and IL-7 in RA patients contributes significantly to the joint inflammation by activating T cells, B cells, and macrophages. The inhibition of IL-7R–mediated immune activation by soluble hIL-7Rα further indicates an important role of IL-7Rα in inflammatory responses in RA, suggesting IL-7Rα as a therapeutic target for immunotherapy in RA.