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Engineered molecule amplifies body's immune response

By altering a molecule called Stat1, which is involved in cellular immune signaling, scientists have succeeded in making the molecule more responsive and thus more efficient. This old protein with a new twist may eventually be used to improve the body's defense against infection.

Stat1 is involved in immune responses that are initiated by proteins called interferons. These proteins are produced by the cells of the immune system in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. Recently, interferon has also been shown to play a role in the body's surveillance against the development of cancer. Because of this role, recombinant interferon is often used for the treatment of certain fibrotic diseases as well as cancers.

Interferon binds to receptors on the surface of the cell, which then use Stat molecules to send signals to the nucleus to increase the expression of genes needed to defend the host against infection. A balance in the amount of Stat signaling caused by interferon is very important.

"When interferon levels are too low, the host is highly susceptible to infection," explains Dr. Michael J. Holtzman of the Washington University School of Medicine in St. Louis, Missouri. "This also applies to Stat1. Children who are born with genetic deficiencies of Stat1 are also very susceptible to infection. In the more severe case, the children die in infancy of fatal viral infections. In less severe cases, they later develop infections due to mycobacteria. When interferon levels are too high, for example during treatment with interferon, there are side effects due to the increased nonspecific response caused by excessive amounts of interferon."

Dr. Holtzman and his colleagues at the Washington University School of Medicine decided to try to improve the body's defense against infection without causing side effects that occur with interferon treatment by engineering a hyper-responsive Stat1 mo
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Source:American Society for Biochemistry and Molecular Biology


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