MFPL: Immune biologist identifies new switch in immune response

Work by Pavel Kovarik and his team at the Max F. Perutz Laboratories of the University of Vienna and the Medical University of Vienna identified the protein CDK8 as a critical regulator of the body’s immune system. The study, published in the journal Immunity, is the result of a 10-year research effort. The identification of CDK8 offers new possibilities for the treatment of disorders of the immune system.

Important switch in immune response identified
The human body has developed complex defense mechanisms to fight infections by viruses and bacteria, which is crucial for our survival. As part of this defense, the immune system recognizes substances that are foreign to our body. Now, research by the group of Pavel Kovarik at the Max F. Perutz Laboratories (MFPL) of the University Vienna and the Medical University Vienna in collaboration with the team of Dylan Taatjes of the University of Colorado identified a yet unknown switch in the immune system. The results are published in the journal Immunity and show that the protein CDK8 is an important player of the immune response and the fight against viral infections.

10 years of research
As soon as our body detects an infection, immune cells start the production of signaling proteins. These so called cytokines activate STAT proteins, which play a central role in the regulation of the immune reaction. They precisely adjust the levels of players of the immune response, crucial to successfully battle viruses and bacteria while leaving our body unaffected. “The immune response is a fascinating example of the complex yet accurately regulated processes that take place in our body”, says study lead Dr Kovarik. “Several years ago it was discovered that STATs are regulated by cytokines in an additional way to the one we knew about. This mechanism marks STATs at a specific site and as such acts as a molecular switch.” However, for over ten years it remained unclear how the mark was attached to STATs. “Our results now clearly show that the protein CDK8 is responsible for this process and that it is required for proper STAT function and fighting virus infection”, adds Kovarik.

A new therapeutic target
This crucial and surprising role of CDK8 makes it a highly attractive target for the development of new therapeutics to treat disorders of the immune system. Kovarik explains: “Sometimes things go wrong in the complex immune reactions that our body coordinates, resulting in the triggering of an immune response without cause, or the absence of a reaction even though it’s needed.” Studying the role of CDK8 in these disorders will establish if it is a suitable target for drugs that could help patients with immune system defects.

Original publication
Joanna Bancerek, Zachary C Poss, Iris Steinparzer, Vitaly Sedlyarov, Thaddäus Pfaffenwimmer, Ivana Mikulic, Lars Dölken, Birgit Strobl, Mathias Müller, Dylan J Taatjes and Pavel Kovarik: CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response. In: Immunity (2013).

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