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

Arthritis Rheum. 2009 Sep;60(9):2595-605. doi: 10.1002/art.24754.


Objective: To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7Ralpha) in patients with rheumatoid arthritis (RA).

Methods: Expression of IL-7Ralpha 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-7Ralpha 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-7Ralpha(bright) and IL-7Ralpha(dim/-) T cells was measured. In addition, we examined IL-7R blockade with soluble human IL-7Ralpha (hIL-7Ralpha) in the prevention of immune activation of peripheral blood mononuclear cells.

Results: We found significantly higher IL-7Ralpha expression in RA and UA synovial tissue than in OA synovial tissue, and the level of IL-7Ralpha 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-7Ralpha. A substantial percentage of B cells and macrophages from RA synovial fluid and synovial tissue also expressed IL-7Ralpha, although less prominently than T cells. We found that peripheral blood IL-7Ralpha(bright) T cells that did not express FoxP3 were highly proliferative as compared with IL-7Ralpha(dim/-) T cells that did express high levels of FoxP3. Soluble hIL-7Ralpha inhibited IL-7-induced proliferation and interferon-gamma production by mononuclear cells from RA patients.

Conclusion: Our data suggest that enhanced expression of IL-7Ralpha 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-7Ralpha further indicates an important role of IL-7Ralpha in inflammatory responses in RA, suggesting IL-7Ralpha as a therapeutic target for immunotherapy in RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / metabolism
  • Arthritis / immunology
  • Arthritis / metabolism
  • Arthritis / pathology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interleukin-7 / metabolism*
  • Joints / immunology
  • Joints / metabolism*
  • Joints / pathology
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Receptors, Interleukin-7 / metabolism*
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology


  • Antigens, CD19
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-7
  • Lipopolysaccharide Receptors
  • Receptors, Interleukin-7