Researchers from the Perelman School of Medicine 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,” says senior author Mitchell A. Lazar, director of the Institute for Diabetes, Obesity, and Metabolism. “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.”
Inflammation is a highly complex defense mechanism employed by the innate immune system, meaning that it’s something someone is born with and not acquired later like other parts of the immune system. Although inflammation is famous for the appearance of swelling, it also includes changes in blood flow and blood vessel permeability and the migration of white blood cells. When well-orchestrated, the inflammatory response should quickly and precisely locate and eliminate danger before subsiding to anti-inflammatory processes that help with the removal of damaged tissues so that the body can begin to heal and repair.
This story is by Frank Otto. Read more at Penn Medicine News.