Press Release

18.04.2013

Related Roquin proteins redundantly control T cell differentiation

Neuherberg, Germany, April 18, 2013. The two genetic variants Roquin-1 and Roquin-2 are crucial for differentiating T cells in the immune response. The proteins that they encode are interchangeable in terms of their molecular function, and defects in the Roquin-1 gene can cause severe autoimmune diseases. For the first time, scientists at the Helmholtz Zentrum München have now analyzed the complex interaction of the two proteins and described their activity as regulators of gene expression. The results have been published in the journal 'Immunity'. .

Image: Prof. Vigo Heissmeyer, Institute of Molecular Immunology

Roquin proteins control the activation and differentiation of T cells by regulating gene expression at the level of the messenger RNA. The function of the RNA-binding proteins is primarily to guarantee immunological tolerance and prevent an excessive immune response, which, for example, occurs in autoimmune diseases.

In their publication, Katharina Vogel and Dr. Stephanie Edelmann from the Institute of Molecular Immunology (IMI) at the Helmholtz Zentrum München (HMGU) were able to demonstrate how the two proteins, Roquin-1 and Roquin-2, can replace each other functionally and which consequences result from the combined loss of both Roquin genes. In the absence of Roquin-1, Roquin-2 compensates for its function. In T cells the proteins are consequently interchangeable as far as their molecular function is concerned, and they fulfill a type of reservoir function for each other. The loss of both Roquin genes results in an uncontrolled accumulation of effector T cells and particularly of follicular helper T cells. If these T cells then trigger an immune response against the body's own structures, a clinical picture results that is similar to that for lupus erythematosus, a severe autoimmune disease that attacks the skin and internal organs. The single point mutation in the Roquin-1 gene, meaning the exchange of a single amino acid in the protein, also leads to such a disease. Interestingly enough, in this case the Roquin-2 protein is unable to take over the function of the defective Roquin-1, resulting in complete loss of the Roquin function. The scientists in the HMGU team, including Prof. Dr. Wolfgang Wurst, Prof. Dr. Mathias Heikenwälder, Dr. Arie Geerlof, Dr. Frauke Neff and Dr. Elisabeth Kremmer, along with Dr. Marc Schmidt-Supprian from the Max Planck Institute of Biochemistry in Martinsried, Germany, were furthermore able to identify the molecular attack structures of the Roquin proteins, Icos and Ox40 messenger RNAs. "This work demonstrates the importance of the Roquin-1- and Roquin-2 proteins for T cell differentiation in immune responses", explained the last author, Prof. Dr. Vigo Heissmeyer, group leader at the IMI and professor at the Institute for Immunology at LMU Munich. "Particularly the regulation of these factors is now of great interest to us, because it can also be used as a therapeutic target in the treatment of autoimmune diseases."

Although follicular helper T cells are involved causatively in the development of autoimmune diseases, they also play an important role in forms of immunodeficiency and in lymphomas and infectious diseases, including HIV. Immunological studies and infection research are a part of the health research being conducted at the Helmholtz Zentrum München. The goal is the rapid enhancement of results from fundamental research in order to provide concrete benefits for society.

Further Information

Original Publication:
Vogel, K. et al. (2013), Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox 40 Costimulator mRNAs and Control Follicular Helper T Cell Differentiation, Immunity, 38, 1-14

Link to publication

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,100 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. www.helmholtz-muenchen.de

The Institute of Molecular Immunology (IMI) conducts application-oriented basic research at the interfaces of hematology, immunology, onkology and transplantational biology. With the help of cell and molecular-biological method of the immune system the immune system can be modulated. A simulation of the immune system should be made useful for the patients, for example, in case of immune- and gene therapy of cancer and autoimmune diseases or of possible transplantation rejections of the immune system.

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Contact for the media
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg - Tel.: +49 89-3187-2238 - Fax: +49 89-3187-3324 -

Specialist contact
Prof. Vigo Heissmeyer, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute of Molecular Immunology, Marchioninistr.25, 81377 München, Germany - Phone: +49-89-3187-1214 -

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