Unveiling the mechanisms of asthma Allergic asthma affects a large proportion of European citizens and despite extensive research, there is no cure available. Understanding the mechanisms that trigger asthma is our best bet for disease management. Health © Thinkstock Asthma is a chronic inflammatory airway disease in which the transcription factor NF-kB plays a crucial role. NF-kB is subject to enzymatic modifications for its activation. Among the enzymes that control NF-kB modification is A20 and mice lacking this enzyme succumb from an autoimmune inflammatory disease. However, the precise role of A20 in asthma has yet to be determined. The key objective of the EU-funded ‘The role of A20 in dendritic cells and mast cells in the allergic immune response’ (A20 IN Allergy) project was to study the function of A20 in a cell-specific context. To achieve this, animals lacking A20 in specific immune cells were generated and studied. Results indicated that A20 deletion in dendritic cells (DCs) did not contribute to disease pathology, despite the fact that A20 was found to mediate control of DC activation via NF-kB. Rather, A20 was shown to play a crucial part in the development of systemic autoimmunity. Mice lacking A20 specifically in mast cells, showed increased airway inflammation and sensitisation to allergens compared to their wild-type littermates, suggesting that adaptive immune responses were important. Given the role of mast cells in the early phase of an allergic reaction, project findings indicated that A20 controlled mast cell activation through NF-kB. Although further experiments are required to fully elucidate the role of A20 in mast cells, A20 IN Allergy outcomes hold high socioeconomic implications. Implementation of results can lead to novel treatment regimens and hopefully substantial reduction in health care costs for asthma sufferers.
