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Press Releases 2006

Discovery of new switch in the immune system: identical enzyme enhances and inhibits immune activation

Dr. Daniel KrappmannThe enzyme IKKβ is not only an activator, but also a deactivator of immune reaction. This surprising discovery is reported by Elmar Wegener and Daniel Krappmann, scientists at the GSF Research Center for Environment and Health, in the well-known scientific journal Molecular Cell.

Dr. Daniel Krappmann, head of the GSF Junior Scientist Group "Signal Processes in the Immune System"
Photo: Ulla Baumgart. [ 300 dpi print resolution download]

It has been known for some time that the kinase IKKβ is part of an indispensable signal cascade in the immune system. IKKβ is needed to pass on signals which eventually initiate the secretion of messenger substances in order to coordinate the immune response of the body to pathogenic viruses or bacteria. "In cooperation with the Technical University of Munich and Harvard Medical School in Boston we could now show that IKKβ can also weaken the immune response and, thus, produce exactly the opposite effect", says Dr. Daniel Krappmann, head of the GSF Junior Scientist Group "Signal Processes in the Immune System". The scientists managed to reveal a new point of attack of the enzyme: IKKβ impedes the function of a protein complex (CBM complex) which normally boosts immune reaction – thus the enzyme attacks at various sites in the signal transfer process. "Only the analysis of the proteome can elucidate such a complex, non-hierarchical interaction of effects. In genetic knock-out studies such dual functions of individual enzymes cannot be detected", emphasizes Krappmann.

The scientists assume that the dual function makes a decisive contribution to the balance of the immune reaction both by boosting it a nd by slowing it down. The newly discovered mechanism of IKKβ could be a therapeutical goal for diseases in which the immune system gets derailed, such as in the case of autoimmune diseases. "We have shown that IKK b can modulate the activity of the CBM complex, so that the immune reaction is brought to a halt or at least weakened considerably. It would now be conceivable to develop a therapy based on this reaction", explains Krappmann. Patients suffering from a particular type of leukaemia, diffuse large B-cell lymphoma, could benefit from such a therapy one day: "Studies conducted by American scientists have shown that it is particularly with an extremely aggressive type of this lymphoma that the activity of the CBM complex guarantees the survival of the diseased cells. Here, too, a modulation of the complex might be a way to intervene", hopes Krappmann.

Further information

Neuherberg, Juli 17., 2006