Tags

Type your tag names separated by a space and hit enter

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.AR

Abstract

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.

Authors+Show Affiliations

Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19714586

Citation

Hartgring, Sarita A Y., et al. "Elevated Expression of Interleukin-7 Receptor in Inflamed Joints Mediates Interleukin-7-induced Immune Activation in Rheumatoid Arthritis." Arthritis and Rheumatism, vol. 60, no. 9, 2009, pp. 2595-605.
Hartgring SA, van Roon JA, Wenting-van Wijk M, et al. Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis. Arthritis Rheum. 2009;60(9):2595-605.
Hartgring, S. A., van Roon, J. A., Wenting-van Wijk, M., Jacobs, K. M., Jahangier, Z. N., Willis, C. R., Bijlsma, J. W., & Lafeber, F. P. (2009). Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis. Arthritis and Rheumatism, 60(9), 2595-605. https://doi.org/10.1002/art.24754
Hartgring SA, et al. Elevated Expression of Interleukin-7 Receptor in Inflamed Joints Mediates Interleukin-7-induced Immune Activation in Rheumatoid Arthritis. Arthritis Rheum. 2009;60(9):2595-605. PubMed PMID: 19714586.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis. AU - Hartgring,Sarita A Y, AU - van Roon,Joel A G, AU - Wenting-van Wijk,Marion, AU - Jacobs,Kim M G, AU - Jahangier,Zalima N, AU - Willis,Cynthia R, AU - Bijlsma,Johannes W J, AU - Lafeber,Floris P J G, PY - 2009/8/29/entrez PY - 2009/8/29/pubmed PY - 2009/10/20/medline SP - 2595 EP - 605 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 60 IS - 9 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/19714586/Elevated_expression_of_interleukin_7_receptor_in_inflamed_joints_mediates_interleukin_7_induced_immune_activation_in_rheumatoid_arthritis_ L2 - https://doi.org/10.1002/art.24754 DB - PRIME DP - Unbound Medicine ER -