Full Throttle on the DNA
How the immune system controls itself: HZI scientists clarify the mechanism
Millions of Germans suffer from autoimmune diseases such as rheumatism, diabetes or chronic intestinal inflammation: the body’s defence system raises a false alarm and starts to attack its own body cells. The reasons for such overreactions are diverse and have not been understood completely until now. Therapies can only cure the symptoms. In collaboration with the Charité in Berlin and the company Epiontis, scientists from the German Helmholtz Centre for Infection Research in Braunschweig (Helmholtz-Zentrum für Infektionsforschung, HZI) have now found that the molecule CCR6, which is located on the surface of immune cells and is responsible for directing them to their site of action, is only produced as required. The responsible gene is activated by removing a chemical tag that usually silences the gene. The results add a new piece to the puzzle of understanding autoimmune diseases and will be of interest for new therapy concepts. The scientific magazine “Blood” has now published the results in its current issue.
Cells communicate with chemical substances that bind receptors on the cell’s surface. They can trigger various reactions. The receptor CCR6 for example is responsible for guiding T cells – a special kind of immune cell – to places of inflammation.
The HZI researchers have now discovered that certain regions on the DNA for the CCR6 gene are chemically modified: when the DNA is tagged with methyl groups, no CCR6 is produced. On the other hand, when the DNA is free of these groups, CCR6 is always present on the cell surface. When an immune cell receives an appropriate signal, it releases the tag from the genes and they become activated.
The cycle of methylation and demethylation is a well-known chemical modification of the DNA, resulting in an inactivation and re-activation of certain gene regions. However, the sequence of the four base pairs in the DNA is not changed but the activity of the affected DNA region is controlled.
“Removing the methyl groups from the DNA functions as a turbo: The cell starts to constantly express CCR6”, says Dr. Stefan Flöß who performed the experiments at the HZI in Braunschweig. In the case the immune system selects the wrong cell to express CCR6, it may have fatal consequences for the immune system and the body. “In autoimmune diseases, the equilibrium of cells enhancing inflammation and those relieving inflammation is disturbed. In such situations dysregulation of CCR6 may play a crucial role”.
“The knowledge of the mechanism of CCR6 regulation may help in the future to improve diagnostics of autoimmune diseases”, says Flöß. “You may be able to check the blood of patients if the presence or absence of CCR6 on the cells’ surfaces correlates with the progress of the disease.”
Publication: Steinfelder S, Floess S, Engelbert D, Haeringer B, Baron U, Rivino L, Steckel B, Gruetzkau A, Olek S, Geginat J, Huehn J, Hamann A., Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells. Blood, 10 March 2011, Vol. 117, No. 10, pp. 2839-2846.