A recent discovery from the Research Institute of the McGill University Health Centre (RI-MUHC) suggests autoimmune and chronic inflammatory diseases may be linked to mutations in a critical gene. The discovery also sheds new light on the function of Regulatory T Cells (Tregs) in the regulation of the immune system.
Tregs play a key role in preventing excessive immune responses. They prevent the body’s immune cells from attacking its own tissues in the presence of non-pathogenic agents and microbes such as dust, pollen and food. The FOXP3 gene, in turn, plays a crucial role in the development and function of Tregs.
AllerGen investigators Drs Moshe BenShoshan, Bruce Mazer and Ciriaco Piccirillo collaborated in the discovery of how a specific mutation in FOXP3 disrupts the ability of Tregs to suppress overreactions by the immune system.
“This discovery gives us key insights on how Treg cells are born and how they can be regulated,” says Dr. Piccirillo, the study’s lead author, in the McGill news release.
The findings, published in the June 2017 issue of Science Immunology, reveal that the FOXP3 mutation disrupts Treg function in individuals with a rare immune disorder called IPEX (immunedysregulation polyendocrinopathy enteropathy X-linked syndrome).
The researchers also found that this disruption can be corrected using allosteric modifiers that enhance FOXP3’s functions—suggesting a potential therapeutic target for other conditions where Treg activity is similarly disrupted.
The discovery was made by analyzing a few drops of blood collected from a fiveweek-old infant who died in 2009 from IPEX.
“What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: their ability to shut down the inflammatory response,” comments Dr. Piccirillo.
The discovery may have implications for other autoimmune and chronic inflammatory and diseases, including asthma and allergies, that may similarly be associated with alterations in FOXP3 functions.
“Our goal is to increase the activity of these Treg cells in certain settings [to treat disease],” further notes Dr. Piccirillo.
“With this discovery, we are taking a big step in the right direction.”