Researchers from The University of Queensland and The Australian National University (ANU) have found that a protein which protects the body from fungal infections is also responsible for making certain diseases like irritable bowel disease (IBS), type 1 diabetes and eczema more severe.
Dr Pablo Canete from UQ’s Frazer Institute said the discovery about the protein, known as DECTIN-1, could pave the way for more effective drugs without the negative side effects of existing treatments.
“We have discovered that DECTIN-1 in its mutated state limits the production of T regulatory cells or so-called ‘guardian’ cells in the immune system,” Dr Canete said.
“These guardian cells are crucial to preventing autoimmune disease because they suppress the effects of a hyperactive immune system, which can be extremely dangerous if not properly regulated.
“The immune system is designed to protect the body from infection, but in severe cases it becomes overactivated and turns the body’s natural defences against itself.”
Lead author Dr Cynthia Turnbull from the Australian National University said when the immune system becomes overactivated, it wrongly perceives healthy cells as a threat and can promote the onset of autoimmune disease.
“Although the DECTIN-1 protein helps to fight fungal infections, in its mutated state it's also responsible for exacerbating severe autoimmune disease,” Dr Turnbull said.
By examining the DNA of a Spanish family, the researchers discovered the DECTIN-1 mutation was responsible for exacerbating the severity of a chronic autoimmune disease suffered by the family’s only child.
“We found the family was also carrying a mutated version of another immune system protein known as CTLA-4.
“The CTLA-4 mutation prevents guardian cells from working properly and is known to cause severe autoimmune disease in about 60 to 70 per cent of people who carry it in their DNA,” Dr Canete said.
“Strangely, the remaining 30 to 40 per cent of the population who carry this mutated protein don’t develop disease.
“We discovered the family’s only child had both the DECTIN-1 mutation and the CTLA4 mutation, while his parents had only one of each.
“This helped us identify why the child, who is now in his twenties, was the only person in the family to develop severe autoimmunity, ending a 20-year-long mystery behind the cause of his disease.
“By discovering the existence of mutated versions of modifier proteins such as DECTIN-1, we finally have an explanation for why some people develop severe autoimmune diseases while others don’t, even if they inherit gene mutations passed down from family members.”
Professor Carola Vinuesa from the Francis Crick Institute said the group believes they can control the immune system by turning the DECTIN-1 protein on and off, like a light switch.
“Turning on the protein would lower the intensity of the immune system’s defensive response which would help to treat conditions such as autoimmune disease,” Professor Vinuesa said.
“On the other hand, turning off the protein could give the immune system a boost, sending its defensive mechanisms into overdrive and allowing the body to treat an entirely different set of diseases.”
According to Dr Turnbull, DECTIN-1 could also play a key role in treating cancer.
“Cancer cells can disguise themselves by releasing certain proteins and chemicals into the body that essentially render them invisible from the immune system’s natural defences,” she said.
"We think that by using drugs to turn off the DECTIN-1 protein, in combination with existing therapies, we can activate the immune system and help it identify and attack the cancerous cells.”
Current treatments for autoimmune disease aren’t very effective and have a lot of damaging side effects because most existing treatments suppress the entire immune system rather than targeting a specific area.
The research is published in Science Advances. It was led by ANU in collaboration with The University of Queensland and the Francis Crick Institute.
Media: UQ Medicine Communications, med.media@uq.edu.au, +61 436 368 746.