Chronic airway inflammation in Drosophila lacking the A20-like protein Trabid

The long-term alteration of epithelial immune homeostasis is central to the development and persistence of chronic lung disease. Regulators of immune pathways, such as the NF-kB pathway, are critical in this context. A20 (tumor necrosis factor-α induced protein 3 (TNFAIP3)) is one of the inhibitors of the NF-κB pathway associated with chronic lung disease. Using the Drosophila A20 ortholog, called Trabid, we have shown that trabid-deficient animals exhibit chronic immune response activation in the airways. In addition, these animals show a significantly increased sensitivity to airborne stressors such as dehydration, chronic cigarette smoke, and hypoxia. Furthermore, these animals lose the ability to respond to hypoxic stimuli with an otherwise observable plastic adaptation of the terminal cells of the tracheal system. In conclusion, the disease-associated changes in A20/trabid deficiency are not only due to increased immune activity in the epithelia but also to a massive reduction in stress resistance. Dissected larval trachea from Trabid knockout animals and corresponding controls were used for transcriptomic analysis.