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Marine sponge leads researchers to immune system regulator

A Japanese brewery, an Okinawan sea sponge and some clever detective work have enabled an international research team based at the University of Chicago to solve a biological mystery, and the solution suggests a novel way to boost the body's defenses against cancer.

In Science Express, the online early-publication version of the journal Science, the researchers provide evidence that a sugary lipid known as iGb3 plays a key role in regulating the response of natural killer T cells, a component of the immune system that plays an important role in preventing cancer, fighting infections and perhaps triggering or avoiding autoimmune diseases.

Discovered less than ten years ago, natural killer (NK) T cells are unusual because they target lipids, often bound to carbohydrates, rather than proteins. When presented with a lipid that may signal a threat, they pump out chemical signals, such interferon-gamma and interleukin-4, which tell other components of the immune system to rid the body of these invaders.

Mice with defects in this system are prone to cancer and susceptible to infections. On the other hand, misdirected NKT cells may play a role in autoimmune diseases, such as type-1 diabetes.

"Until now we had no idea what activated NKT cells except for one curious compound, a glycosphingolipid derived from a marine sponge," said study author Albert Bendelac, "but once we learned that this compound could prevent the spread of cancer in mice, a lot of people became very interested."

Bendelac, M.D., Ph.D., a professor of pathology at the University of Chicago, is one of only a handful of immunologists who concentrate on NKT cells. Scientists know a great deal about how the immune system recognizes proteins, but comparatively little about this type of cell or the mechanisms the immune system uses to sort out lipids.

NKT cells are also odd in that they fall somewhere between the brute force of innate immunity and the f
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
11-Nov-2004


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