Investigating the role of T cells in rheumatoid arthritis

Main Category: Arthritis / Rheumatology
Article Date: 02 Dec 2004 - 10:00 PDT


Rheumatoid arthritis is a chronic inflammatory disease leading to joint destruction. Considered by some to be an autoimmune disorder where immune complexes are formed in the joints and excite an inflammatory response, various genetic, environmental, and infectious agents have been suggested as causes of the disease. IL-1 is a proinflammatory molecule produced by cells of the immune system and cells lining the joints and it has been suggested that IL-1 may have a role in the development of RA.

The body also produces a natural inhibitor to IL-1, IL-1 receptor antagonist (IL-1Ra), the levels of which are augmented in patients with autoimmune and inflammatory diseases. Another proinflammatory agent, TNF-a, stimulates IL-1 expression and vice versa.

In the December 1 issue of the Journal of Clinical Investigation, Yoichiro Iwakura and colleagues from the University of Tokyo studied the role of T cells in the development of autoimmune arthritis in mice lacking IL-1Ra.

The authors demonstrated that mice deficient in both T cells and IL-1Ra did not develop arthritis. Arthritis development also appeared to be markedly decreased in cases of TNF-alpha deficiency.

The authors found that IL-1Ra produced by these T cells act on the T cells themselves to induce TNF-alpha expression and TNF-alpha in turn induces OX40 expression on T cells. As inhibition of TNF-a or OX40, the latter being an activation antigen on T cells, which invade tissues and cause autoimmune destruction - was effective in suppressing the development of arthritis, the authors suggest that their study may provide a clue for the development of new therapies for RA.

TITLE: TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

AUTHOR CONTACT:
Yoichiro Iwakura
Center for Experimental Medicine
University of Tokyo
Tokyo, Japan
Phone: 81-3-5449-5536
Fax: 81-3-5449-5430
E-mail: iwakura@ims.u-tokyo.ac.jp.
View the PDF of this article at: https://www.the-jci.org/press/20742.pdf

Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-0497
Journal of Clinical Investigation

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