Researchers from the Perelman School of Medicine at the University of Pennsylvania have now identified a protein called histone deacetylase 3 (HDAC3) as the orchestrator of the immune system’s inflammation response to infection. By using both specially cultured cells and small animal models, HDAC3 was found to be directly involved in the production of agents that help kill off harmful pathogens as well as the restoration of homeostasis, the body’s state of equilibrium. This work, published in Nature, shows that some of the methods being tested to fight cancer and harmful inflammation, such as sepsis, that target molecules like HDAC3 could actually have unintended and deadly consequences.
“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, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism (IDOM). “Now that we understand this, it is now much clearer what needs to be targeted when medications are tested and used to counter potentially deadly inflammation.”