JUL 07, 2017 3:09 PM PDT

FOXP3 Mutations Lead to Autoimmune Disease, But Scientists Have An Answer

WRITTEN BY: Kara Marker

Thanks to regulatory T cells (Tregs), the immune system is kept in line via a careful system of checks and balances. Immune response too light? A viral infection spreads throughout the body. Immune response too heavy? Autoimmune disease. From research in the past, scientists found that mutations in a gene called FOXP3 disrupted the Treg-coordinated immune balance. But now a study from the McGill University Health Centre finally digs into how.

A lymph node with  normal T cells (red) and Treg cells regulated by the FOXP3 gene (green). Credit: Ciriaco Piccirillo, Research Institute of the McGill University Health Centre

A mutation in FOXP3 prevents Tregs from suppressing the immune response at appropriate times, leading to an overactive response characteristic of autoimmune disease. "This discovery gives us key insights on how Treg cells are born and how they can be regulated,” said lead author Dr. Ciriaco Piccirillo.

Using just a few drops of blood from a five-week old newborn baby boy who was born with IPEX, a rare inherited genetic immune disorder. The baby, born in 2009, didn’t make it. "What was unique about this case of IPEX was that the patient's Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response," Piccirillo said.

Unsurprisingly, IPEX is caused by FOXP3 mutations, leading to Treg dysfunction and immune failure; nearly 60 mutations in the gene can cause IPEX. In nearly 40 years, only 200 cases of IPEX have been identified.  "Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions," explained first author Khalid Bin Dhuban.

Miraculously, McGill University scientists are already working on and testing a cure for various conditions that result from a FOXP3 genetic alteration, making up for the deleterious mutation by manually returning Treg activity - preventing an immune overreaction - to its former glory.

Arthritis, lupus, multiple sclerosis (MS), and type 1 diabetes are among the immune-related conditions to with these studies could apply. Current methods of treating overzealous immune responses that cause autoimmune disease include suppressing the immune system altogether. But even when a person has an autoimmune disease, they still need protection against things like infection and cancer, so this method is flawed.

“Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer,” Piccirillo said. “With this discovery, we are taking a big step in the right direction."

The present study was published in the journal Science Immunology.

Source: McGill University Health Centre

About the Author
Master's (MA/MS/Other)
I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
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