Scientists from Umeå University and University of Gothenburg have identified a molecular switch (MYSM1) that can suppress an overreaction by the immune system and avoid inflammation. The study (“Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes”) is published in Immunity.

“The discovery of MYSM1 [a molecule in the nucleus of resting cells] is a major milestone in our understanding of how our immune system works, and how its response could be controlled in order to prevent inflammatory diseases such as sepsis,” says Nelson O. Gekara, Ph.D.,  research leader at Molecular Infection Medicine Sweden at Umeå University.

The innate immune system is activated when our body needs to protect itself against pathogens, for instance bacteria and viruses, as well as for tissue healing. In some people, the immune system overreacts, which can cause chronic inflammatory diseases and result in tumor development. The innate immune system is activated by receptors that recognize certain molecular patterns found on microbes or dead cells. These receptors are called pattern-recognition receptors (PRRs).

“Most infectious or inflammatory situations are associated with the simultaneous or sequential activation of multiple PRR pathways. Therefore, it is essential to avert a disproportionate self-destructive immune response in a synchronized fashion once activated. How this is accomplished has been unclear,” continues Dr. Gekara.

For the first time, the researchers are now able to show that during infection or inflammation MYSM1 accumulates outside of the nucleus and in the cytoplasm where it disrupts the function of signaling molecules involved in activation of PRR pathways, thereby terminating inflammation.

“MYSM1 can be said to act like a molecular switch that can turn off several inflammatory pathways. Therefore lack of MYSM1 in animal results in unrestrained activation of the innate immune system, leading to inflammatory diseases” says Dr. Gekara.

His research team is now screening for small molecule compounds that are able to modulate the MYSM1 molecule activity. The hope is to find new therapeutics against infections and other inflammatory diseases.

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