In a study published online in March 2007 in the Proceedings of the National Academy of Science, researchers at the University of Pennsylvania School of Medicine have discovered how to modify enzymes that act on the FOXP3 protein, in turn making the regulatory immune cells work better. The team was lead by Bin Li, PhD.
The FOXP3 protein is found in immune cells, and when the gene that encodes the protein undergoes a mutation, the immune cell containing the protein can lose its ability to operate Ð often leading to select forms of arthritis. Li and his team discovered that the FOXP3 protein works via a complex set of enzymes. One set of those enzymes are called histone deacetylases, or HDACs. These enzymes are linked to the FOXP3 protein in association with another set of enzymes called histone acetyl transferases that modify the FOXP3 proteins.
Furthermore, Li found that when the histone acetyl transferases are active, or when the histone deacetylases are inactive, the immune regulatory cells work better and longer. As a consequence of the action of the acetylating enzyme, the FOXP3 protein functions to turn off pathways that would lead to autoimmune diseases.
By following a simple approach of moderating the activity of HDACs, the team thinks that the treatment of autoimmune diseases in humans will be revolutionize. At the moment, only non-specific therapies exist to treat most detrimental autoimmune responses. Now, however, scientists and doctors have a set of specific enzymatic drug targets that can regulated chemically.
Li and his Penn colleagues, along with Mark Greene, MD, PhD, the John Eckman Professor of Pathology and Laboratory Medicine, are now extending this research directly to several mouse models of autoimmune diseases.