Inhibiting an enzyme called SUV39H1 in mice limited the development of allergic asthma—an effect that might be translatable to humans, according to investigators.
(Click here to listen to a Pulmonary Reviews audiocast in which Rhys Allan, PhD, discusses his DNA research in a mouse model of allergic asthma.)
In a mouse study, inhibiting an enzyme called SUV39H1 affected the DNA of T helper 2 (Th2) cells and limited their ability to promote allergic asthma, according to a report in the July 12 Nature. This finding suggests that SUV39H1 could be a target of treatments for allergic asthma and other obstructive pulmonary diseases in humans, the researchers said.
“In cases of allergic asthma or other Th2 inflammatory diseases, there can definitely be an advantage in using the inhibitor of this enzyme,” Rhys Allan, PhD, of the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, told Pulmonary Reviews. “We’re doing preliminary work in mouse models, so it needs to be tested in other organisms. But we know this enzyme has an important role in humans, as well. So, yes, we think that the work should be translatable.”
Allan and colleagues performed their research at Institut Curie Research Center in Paris.
The researchers set out the investigate which enzymes are involved in silencing or activating gene regulatory networks that control T helper cells, Allan said. They focused specifically on Th2 cells because these cells are known to promote allergic asthma.
Through in vitro studies, the researchers found that SUV39H1 plays an important role in controlling the function of Th2 cells by silencing the cells’ alternative pathways, such as T helper 1 (Th1) genes. “Then, by using a mouse model of allergic asthma, we basically found that the Th2 cells, when they were lacking this enzyme, were destabilized, and they weren’t able to promote allergic asthma to the same extent that normal Th2 cells were able to,” Allan said.
Next, the researchers used an inhibitor of SUV39H1 in mice. “We added the inhibitor at the time of sensitization to the antigen and into the intranasal pathway,” Allan explained. “We found that every time we used it, we saw a reduction in the mucus production in the airways. The immune response was skewed toward the Th1 response, rather than being solely focused on Th2 response, as it normally is.” When SUV39H1 is inhibited, cells may be unable to recruit eosinophils and other allergy-promoting immune cells into the airways, he suggested.
There will need to be a number of additional animal studies before SUV39H1 inhibition can be tested as an asthma treatment for humans, Allan said.
In the meantime, his team is focusing on other components of epigenetic circuitry. “There are many different enzymes which play very important roles in gene regulation,” Allan said. “And the beauty of this is that there can always be inhibitors of the enzymatic function.”
Allan RS, Zueva E, Cammas F, et al. An epigenetic silencing pathway controlling T helper 2 cell lineage commitment. Nature. 2012;487(7406):249-253.