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Discovering immune system’s “switch”

Medicine@Yale, 2013 - November

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When the immune system kicks into action, more immune cells usually mean a faster elimination of the invading bacteria or virus. But when the reaction continues for too long or becomes overblown, excessive inflammation or even autoimmune disease can occur. And scientists may now have a better idea why.

In the July 25 issue of Immunity, Carla V. Rothlin, Ph.D., assistant professor of immunobiology, and colleagues describe a negative feedback cycle between dendritic cells—early responders to pathogens—and the T cells they activate. Activated T cells, the team showed, produce a molecule called Protein S that then turns down the activity of dendritic cells.

This cycle explains how the immune system is regulated in healthy individuals, and also offers new clues about autoimmune diseases like inflammatory bowel disease (IBD), where activation is more constant. When the team tested patients with IBD, they found less Protein S than in healthy controls, suggesting the cycle may be disrupted in cases of disease.

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