Ms Willis, Ms Alcorn, and Ms Nelson own stock or stock options in Amgen Inc.
Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators
Article first published online: 24 MAY 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 9, pages 2716–2725, September 2010
How to Cite
Hartgring, S. A. Y., Willis, C. R., Alcorn, D., Nelson, L. J., Bijlsma, J. W. J., Lafeber, F. P. J. G. and van Roon, J. A. G. (2010), Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators. Arthritis & Rheumatism, 62: 2716–2725. doi: 10.1002/art.27578
- Issue published online: 31 AUG 2010
- Article first published online: 24 MAY 2010
- Manuscript Accepted: 18 MAY 2010
- Manuscript Received: 6 JUL 2009
To study the effects of interleukin-7 receptor α-chain (IL-7Rα) blockade on collagen-induced arthritis (CIA) and to investigate the effects on T cell numbers, T cell activity, and levels of proinflammatory mediators.
We studied the effect of anti–IL-7Rα antibody treatment on inflammation and joint destruction in CIA in mice. Numbers of thymocytes, splenocytes, T cell subsets, B cells, macrophages, and dendritic cells were assessed. Cytokines indicative of Th1, Th2, and Th17 activity and several proinflammatory mediators were assessed by multianalyte profiling in paw lysates. In addition, T cell–associated cytokines were measured in supernatants of lymph node cell cultures.
Anti–IL-7Rα treatment significantly reduced clinical arthritis severity in association with reduced radiographic joint damage. Both thymic and splenic cellularity were reduced after treatment with anti–IL-7Rα. IL-7Rα blockade specifically reduced the total number of cells as well as numbers of naive, memory, CD4+, and CD8+ T cells from the spleen and significantly reduced T cell–associated cytokines (interferon-γ, IL-5, and IL-17). IL-7Rα blockade also decreased local levels of proinflammatory cytokines and factors associated with tissue destruction, including tumor necrosis factor α, IL-1β, IL-6, matrix metalloproteinase 9, and RANKL. IL-7Rα blockade did not significantly affect B cells, macrophages, and dendritic cells. B cell activity, indicated by serum anticollagen IgG antibodies, was not significantly altered.
Blockade of IL-7Rα potently inhibited joint inflammation and destruction in association with specific reductions of T cell numbers, T cell–associated cytokines, and numerous mediators that induce inflammation and tissue destruction. This study demonstrates an important role of IL-7R–driven immunity in experimental arthritis and indicates the therapeutic potential of IL-7Rα blockade in human arthritic conditions.