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FOXP3 Gene Mutations May Explain Immune System Excitability in MS and Other Diseases

July 13, 2017

Scientists at the Research Institute of the McGill University Health Centre reported that a gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases, like multiple sclerosis (MS). The study was published in the journal, Science Immunology, and is titled, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions.” According to the study, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Tregs are the immune systems players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. Mutations prevent Tregs from performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. The FOXP3 gene is known to be essential for proper Treg cell function.

In the study, the research team in collaboration with other researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan, evaluated the impact of a FOXP3 gene mutation in autoimmunity response. The team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. They found that the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. The team developed a compound capable of restoring Treg cells ability to control the immune system in the presence of this specific FOXP3 gene mutation. The compound reduced inflammation and restored normal Treg function in animal models of colitis and arthritis. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including MS, type 1 diabetes, and lupus.

“This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Ciriaco Piccirillo, the study’s lead author and an immunologist in the Infectious Disease and Immunity, Global Health Program, at the RI-MUHC said. “With this discovery, we are taking a big step in the right direction.”