A protein in the immune system that is programmed to protect the body from fungal infections is also responsible for worsening the severity of certain autoimmune diseases such as irritable bowel disease (IBS), type 1 diabetes, eczema and other chronic disorders, according to new research from The Australian National. University (ANU) found.
The discovery could pave the way for new and more effective drugs, without the unpleasant side effects of existing treatments. In addition to helping manage serious autoimmune conditions, the discovery could also help treat all types of cancer.
Scientists have discovered a previously unknown function of the protein, known as DECTIN-1, which in its mutated state limits the production of regulatory T cells, or so-called “guardian” cells in the immune system.
These guard cells are crucial in preventing autoimmune disease because they suppress the effects of an overactive 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 overactive and turns the body’s natural defenses against it.
“When this happens, the immune system mistakes healthy cells as a threat, so it attacks the body and promotes the onset of autoimmune disease,” said lead author Dr Cynthia Turnbull, from ANU.
“Although the DECTIN-1 protein helps fight fungal infections, in its mutated state it is also responsible for worsening severe autoimmune disease.
“Understanding how and why the mutated version of this protein causes autoimmunity in patients brings us one step closer to developing more effective drugs and offers new hope to more than a million Australians suffering from some form of autoimmune disease.”
Scientists believe they can control the immune system by turning the DECTIN-1 protein on and off, like a light switch.
“Activating the protein would reduce the intensity of the immune system’s defense response which would help treat conditions such as autoimmune disease,” said Professor Carola Vinuesa, from the Francis Crick Institute.
“On the other hand, deactivating the protein could boost the immune system, sending its defense mechanisms into overdrive and allowing the body to treat a whole different set of diseases.
“The findings are exciting because there haven’t been many discoveries of so-called modifier proteins like DECTIN-1, which can change the way the immune system behaves to the extent that it can either cause disease or prevent it.
According to Dr Turnbull, this means DECTIN-1 could play a key role in cancer treatment.
“Cancer cells can disguise themselves by releasing certain proteins and chemicals into the body that essentially make them invisible to the immune system’s natural defenses,” he said.
“We believe that by using drugs to disable the DECTIN-1 protein, in combination with existing treatments, we can activate the immune system and help it to locate and attack cancer cells.”
Current treatments for autoimmune disease are not very effective and have many harmful side effects. This is because the majority of existing treatments suppress the entire immune system rather than targeting a specific area.
“This means it may not fix the exact problem behind the patient’s disease and could inadvertently make them vulnerable to infections. Many people on these types of treatments also get bacterial, fungal and viral infections that can worsen their autoimmunity. “, Professor Vinuesa said.
By examining the DNA of a Spanish family, researchers discovered that the DECTIN-1 mutation was responsible for worsening the severity of a chronic autoimmune disease suffered by the family’s only child.
“We found that the family also carried a mutated version of another immune system protein known as CTLA-4. The CTLA-4 mutation prevents sentinel cells from working properly and is known to cause severe autoimmune disease in about 60 to 70 percent of people who carry it in their DNA,” said Dr Pablo Canete, from the University of Queensland.
“Surprisingly, the remaining 30 to 40 percent of the population that carries this mutated protein does not develop disease.
“We discovered the only child in the family had both the DECTIN-1 mutation and the CTLA4 mutation, while his parents had only one of each. This helped us determine why the child, now in his twenties, was the only person in the family to develop severe autoimmune disease, ending a 20-year mystery behind the cause of his illness.
“By discovering the existence of mutated versions of modifier proteins like DECTIN-1, we finally have an explanation for why some people develop severe autoimmune diseases while others do not, even if they inherit gene mutations passed down from family members.”