Elevated expression of interleukin‐7 receptor in inflamed joints mediates interleukin‐7–induced immune activation in rheumatoid arthritis

Wiley - Tập 60 Số 9 - Trang 2595-2605 - 2009
Sarita A. Y. Hartgring1, Joël A. G. van Roon2, M. Wenting-van Wijk2, Kim M G Jacobs2, Z. N. Jahangier2, Cynthia R. Willis3, J. W. J. Bijlsma2, Floris P. J. G. Lafeber2
1Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
2University Medical Center Utrecht, Utrecht, The Netherlands
3Amgen Inc., Seattle, Washington

Tóm tắt

AbstractObjectiveTo evaluate the expression and functional ability of the high‐affinity interleukin‐7 receptor (IL‐7Rα) in patients with rheumatoid arthritis (RA).MethodsExpression 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.ResultsWe 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.ConclusionOur 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.

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Wiley

Tập 60 Số 9

2595-2605

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