(Vienna, 28 September 2018) The 18 members of the histone deacetylase family (HDACs) are important epigenetic factors that regulate cell development and differentiation. Wilfried Ellmeier from the Division of Immunobiology (Institute of Immunology at the Center for Pathophysiology, Infectiology and Immunology) and Christian Seiser from the Division of Cell and Developmental Biology (Center for Anatomy and Cell Biology) have now written a review about the role of HDACs in CD4+ T cells in leading journal "Nature Reviews Immunology" (Impact Factor 41.98).
HDACs control the acetylation status of histones and many other cellular proteins, thus modulating the chromatin function and the activity of non-histone proteins. Pan-HDAC inhibitors are used to treat certain types of cancer. Preclinical data in animal models indicate that the modulation of HDAC activity could also be beneficial in the treatment of T cell-mediated autoimmune diseases. However, at the moment, the side-effects of pan-HDAC inhibitors still outweigh the potential benefits for the treatment of immune-mediated diseases.
In their article, Ellmeier and Seiser not only summarise the latest findings in this field but also discuss important open research questions and put forward the idea that isoform-selective HDAC inhibitors, with potentially fewer side-effects, could extend the clinical application range of HDAC inhibitors to include T cell-mediated autoimmune diseases.
Wilfried Ellmeier and Christian Seiser have been researching these molecules in T cells for many years and have shown, for example, that the integrity of CD4+ T cells is regulated by HDAC1 and HDAC2 (Nat. Immunol. 15(5):439-448), that HDAC1 has a protective role in inflammatory respiratory tract diseases (J. Immunol, 185(6):3489-97), and also that HDAC1 is an important factor that regulates the development of autoimmune diseases (J. Autoimmunity, 86:51-61).
Say the two scientists: "In the age of ultra-modern proteomic and Next Generation Sequencing technologies, it will ultimately be possible to create an integrative model of HDAC function in CD4+ T cells under (patho)physiological conditions. That could also provide a basis for developing and using new isoform-selective HDAC inhibitors for treating T-cell-mediated autoimmune diseases."
Service: "Nature Reviews Immunology“
“Histone Deacetylase Function in CD4+ T cells” Wilfried Ellmeier & Christian Seiser, Nature Reviews Immunology, 2018. doi: 10.1038/s41577-018-0037-z
Link zum Paper: http://www.nature.com/articles/s41577-018-0037-z