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Disabling gene defuses rheumatoid arthritis in mice

Scientists studying mice have identified a gene that allows immune cells known as neutrophils to protect themselves from the inflammatory chemicals they secrete.

Researchers at Washington University School of Medicine in St. Louis showed that knocking the gene out in mice prevented the development of an arthritis-like disorder by making the neutrophils victims of their own damaging secretions.

The newly identified role for the gene, Foxo3a, may open a new window for treating arthritic conditions caused by immune dysfunction. Currently, most treatments in development for these disorders focus either on preventing wayward immune cells from attacking the joints or on reducing the ability of these cells to open fire. The new results suggest it may be just as helpful to let these cells kill themselves and each other.

"We already know a great deal about Foxo3a from studies of its role in some cancers, and hopefully that puts us in a good position to devise ways to manipulate its activity," says senior author Stanford Peng, M.D., Ph.D., assistant professor of medicine and of pathology and immunology. "If the human version of this gene functions in a similar fashion, modifying its activity may be a useful approach for arthritis therapy even when the disease is already well underway."

Peng and colleagues will publish their results in the June issue of Nature Medicine.

Rheumatoid arthritis, the most prevalent autoimmune form of arthritis, afflicts approximately 2.1 million Americans or about 1 percent of the population. Women are two to three times more likely to develop the disorder than men. Symptoms often occur in episodic bursts and may include morning stiffness, fatigue and joint and muscle pain. In severe cases, rheumatoid arthritis can damage cartilage, tendons, ligaments and bone, leading to joint deformity and instability.

Rheumatoid arthritis has long been recognized as a condition that involves defensive cells from the
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Source:Washington University School of Medicine


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