Study Reveals the Two Sides of an Immune Molecule

Scientists have discovered a key protein that regulates the immune system to fight off infections. Fascinatingly, the protein called histone deacetylase 3, or HDAC3, plays seemingly contradictory roles in orchestrating the innate immune response, both initiating it as well as pumping the brakes to restore a state of equilibrium.

The study was published in the journal Nature and has important implications in how we can treat an array of inflammatory conditions beyond infection, including cancer. 

“Our work shows that HDAC3 is key to the innate immune response due to the yin and yang of its responsibilities – both triggering and reducing inflammation,” said senior author, Mitchell A. Lazar, from Penn Medicine. These results provide drug developers with a blueprint for designing precision medicines for countering potentially deadly inflammation.

Lazar and team used a suite of advanced genomic technologies to dissect the intricate function of HDAC3, which acts as an enzyme, catalyzing an array of different immune reactions. Interestingly, the scientists found that HDAC3 functioned much like a light switch. In the “on” position, the enzyme triggered inflammation, while in the “off” state, it repressed it.

The study’s lead author, Hoang C. B. Nguyen, suggests HDAC inhibitors currently in development for treating cancer and inflammation will have to be scrutinized as a result of this new information. “It has been the tradition to target the enzymatic functions of HDAC molecules for decades, but we want to bring attention to the non-enzymatic functions that should be targeted instead,” Nguyen said. 

“In the words of Confucius himself, who introduced the Yin and Yang system of philosophy, ‘Do not use a cannon to kill a mosquito,’ as it might do more damage than good.”

Source: Penn Medicine News, Nature.