Researchers from the University of Bonn have isolated a specific substance that may control contact allergies. The study illuminates the workings of a central immune mechanism that may also play a role in other inflammatory diseases such as arthritis and arteriosclerosis.
The newly discovered substance is an RNA aptamer. Aptamers bind to specific proteins and thereby block them.
“Our aptamer interferes with the communication between two important types of immune cells – T-cells and dendritic cells,” says Dr Irmgard Förster, who heads the department of Immunology and Environment at the LIMES Institute of the University of Bonn.
Allergies occur when the immune system reacts in an uncontrolled way against otherwise harmless substances from the environment. Among other culprits, T-cells are responsible for the resulting damage. These guardians of the immune system normally kill diseased cells, such as those infected by a virus. Patrolling T-cells are activated by so-called dendritic cells, which are distributed throughout the body and sense signs of an infection or tissue damage. If they find something suspicious, they attract the T-cells by releasing certain proteins (chemokines) that steer them to the source.
In humans there are about 50 different types of these signaling chemokines, one of them being CCL17. T-cells have a receptor that can “smell” CCL17 – the CCR4 receptor.
Things go wrong when a harmless protein (an allergen) sets off this cascade of events, causing the T-cells to attack (an allergic reaction.) CCL17 is implicated in these reactions.
“We have succeeded in producing an aptamer that specifically binds to CCL17,” explains Profesor Förster. “It thus prevents CCL17 from docking to the CCR4 receptor. This way, we were able to partly block the migration of T-cells to the dendritic cells. Mice treated with the aptamer therefore showed a far weaker inflammatory response to a contact allergen.”
The problem is that another chemokine, CCL22, seems to have the opposite effect when binding to the CCR4 receptor: it inhibits a reaction. So blocking the CCR4 receptor may actually worsen a reaction.
“Using aptamers, such mechanisms can be explored much more precisely,” says Dr Günter Mayer, a chemist who led the study together with Dr Förster and heads the Center for Aptamer Research and Development at the LIMES Institute. “At present, we are able to produce aptamers comparatively simple and fast, with an astounding specificity for certain target structures,” he says. The current aptamer is a good example: In even the smallest amounts it efficiently neutralizes CCL17, while completely ignoring CCL22.
The study highlights the importance of the chemokine-dependent communication between T-cells and dendritic cells in the context of allergy, and potentially also in autoimmune disorders such as rheumatism and atherosclerosis. The researchers now aim to develop a similar aptamer against human CCL17 to be able to translate their findings from the animal model to clinical application.