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Chromatin-modifying enzyme influences asthma

(Vienna, 31 August 2010) Two research groups at MedUni Vienna have now been able to prove in a model experiment that a specific enzyme has a decisive effect on the development of inflammation with asthma. This finding brings new perspectives to the development of therapeutic agents in the area of immune diseases. The work has now also been published in the renowned Journal of Immunology.

The human immune system is based on an active exchange of information among the cells as there is a coordinated reaction to foreign germs or pathologically modified cells. Here the DNA information contained in the cells has to be read, and this is often regulated via so-called "epigenetic" processes (i.e. via the "degree of packing" of the DNA). Special enzymes, the so-called histone deacetylases (HDACs), play a decisive role here. They determine the "degree of packing", i.e. how efficiently the information can be read. If the "degree of packing" is loosened, the DNA can be read more easily and the communication of the cells is thus stimulated.

In the immune system this can be seen above all from the increased occurrence of special immune defence cells, the T cells (T lymphocytes). The working groups of Univ. Prof. Mag. Dr. Wilfried Ellmeier and Ao. Univ. Prof. Dr. Christian Seiser have now examined the role of the histone deacetylase HDAC1 in the regulation of the development and function of these T lymphocytes and discovered that when the enzyme HDAC1 is missing, certain genes are packed more loosely and can therefore be read better/more efficiently in T-cells.

In an experimental mouse asthma model carried out at MedUni Vienna this led to increased inflammation of the respiratory tract, which is characterised by a migration of leukocytes to the immune defence (eosinophilic granulocytes), increased mucus production and higher airway resistance. The scientists were thus able to show that HDAC1 can regulate the extent of an immune response. This observation may be important in particular for the development of therapeutic agents for diseases which require an enhanced immune response. This is also underlined by the publication of the study in the internationally renowned "Journal of Immunology".

This medically relevant result of the research project funded by the Austrian Science Fund FWF and the Vienna Science, Technology and Research Fund WWTF has been possible in particular thanks to the good cooperation of the two teams of Wilfried Ellmeier from the Institute of Immunology (Centre for Pathophysiology, Infectiology and Immunology) and Christian Seiser from the Division of Molecular Genetics at the Max F. Perutz Laboratories of the Medical University of Vienna, and also thanks to outstanding collaboration with the working group of Dr. Michelle Epstein (Department of Dermatology), as both researchers emphasise particularly.


References:
Conditional Deletion of Histone Deacetylase 1 in T cells Leads to Enhanced Airway Inflammation and Increased Th2 Cytokine Production
Grausenburger, R, Bilic, I., Boucheron, N., Zupkovitz, G., El-Housseiny, L., Tschismarov, R., Zhang, Y., Rembold, M., Gaisberger, M., Hartl, A., Epstein, M.M., Matthias, P., Seiser, C., Ellmeier, W.
» Journal of Immunology 2010, doi:10.4049/jimmunol.0903610.