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Immune system's attack dogs kept on genetic leash

St. Louis, Feb. 12, 2004 -- When they're not busy battling invaders, some of the cells that act as the attack dogs of the mouse immune system have to be kept on a genetic leash to prevent them from mounting inappropriate attacks on the mouse's own tissues, researchers from Washington University School of Medicine in St. Louis have found.

The findings, reported in this week's issue of Science, are the first scientific proof of a theory that could open up a significant new front in the battle to control autoimmune diseases like lupus, multiple sclerosis and diabetes.

"We used to think of mature immune cells like T cells and B cells as metabolically inactive when waiting for infections or other signals that trigger an attack," says Stanford Peng, M.D., Ph.D., assistant professor of internal medicine and of pathology and immunology. "We're now thinking these resting cells actually are very metabolically active, and they are kept in a quiescent state by genes actively working to shut down activating proteins."

In the new study, Peng and colleagues showed for the first time that a gene, Foxj1, helps keep immune attack cells inactive. If malfunctions in this gene and others contribute to human autoimmune diseases, researchers may be able to develop new treatments that restore the genes' functions and ease patients' symptoms.

"Our efforts to develop new treatments have been focused on pathological targets in autoimmune diseases -- genes that are overused or are used inappropriately, leading to immune system attacks on self," Peng explains. "Another concept we should keep in mind is that the loss of one of these regulatory genes that keep the immune system in check also may be a primary contributing factor."

Peng notes, though, that errors in regulatory genes are unlikely to be the sole cause of a particular autoimmune disorder.

"You probably need multiple malfunctions in different genes to cause a severe autoimmune syndr
'"/>

Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
12-Feb-2004


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