Protein Found to Manage Autoimmune Conditions and Potentially Target Cancer

New discovery offers hope to those with autoimmune diseases.

Cynthia Turnbull holds up a 3D printed stencil of a DECTIN-1 structure in a lab at ANU in Canberra, ACT, Australia, Dec. 1, 2023. Tracey Nearmy/ANU

Researchers at the Australian National University (ANU) have identified a potential breakthrough in managing severe autoimmune conditions and treating cancer through a protein in the immune system.

DECTIN-1, typically beneficial against fungal infections, was found to exacerbate autoimmune diseases like irritable bowel disease, type 1 diabetes, and eczema when mutated.

This mutation hampers the production of T regulatory cells, which are crucial for preventing autoimmune diseases.

Lead researcher Cynthia Turnbull explained that these cells suppress the effects of a hyperactive system, which can be dangerous if not properly regulated.

“When the immune system wrongly perceives healthy cells as a threat it attacks the body and promotes the onset of autoimmune disease,” Ms. Turnbull said.

“Although the DECTIN-1 protein helps to fight fungal infections, in its mutated state it is also responsible for exacerbating severe autoimmune disease.

“Understanding how and why the mutated version of this protein causes autoimmunity in patients brings us a step closer to developing more effective drugs.”

How It Works

The scientists propose that DECTIN-1 can be manipulated like a switch to regulate the immune system.

“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,” co-author Carola Vinuesa from the Francis Crick Institute 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.

“The findings are exciting because there haven’t been many discoveries of so-called modifier proteins such as DECTIN-1, which can change the way the immune system behaves to the extent it can either cause a disease or prevent it.”

Ms. Turnbull suggests that this means DECTIN-1 could be crucial 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.”

Cynthia Turnbull in a lab at ANU in Canberra, ACT, Australia, Dec. 1, 2023. Tracey Nearmy/ANU

Current autoimmune disease treatments such as antibiotics are not very effective and have many side effects. This is because they suppress the entire immune system rather than targeting a specific area of the body.

“That means it might not fix the exact problem behind the patient’s disease and could inadvertently make them vulnerable to infections. Many people on these kinds of treatments also get bacterial, fungal, and viral infections which can make their autoimmunity worse,” Ms. Vinuesa said.

However, the discovery could pave the way for drugs with fewer side effects, offering new hope to more than one million Australians who suffer from some form of autoimmune disease.

20-Year Autoimmune Mystery

The researchers’ study involved a DNA analysis of a Spanish family, revealing that a DECTIN-1 mutation worsened a chronic autoimmune disease in the family’s only child.

The family also carried a mutated CTLA-4 protein known to cause severe autoimmune disease in the majority of carriers.

Strikingly, 30 to 40 percent of people with this mutation do not develop the disease.

“We discovered the family’s only child had both the DECTIN-1 mutation and the CTLA-4 mutation, while his parents had only one of each,” said Mr. Pablo Canete from the University of Queensland.

“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.”

Empowering the Immune System Naturally

Meanwhile, some health experts advocate for alternative ways to supercharge your immune system, believing that pharmaceutical drugs may suppress the immune system’s natural response to illness, and carry with it potential adverse effects.

For instance, medications such as dicyclomine for irritable bowel disease, are generally safe but can cause dry mouth, constipation, and blurred vision.

Studies show that irritable bowel disease patients experience an improvement in diarrhea symptoms when they stop eating high-gas foods and drinks, such as alcoholic beverages, carbonated drinks, and gluten, even if they do not have a diagnosis of celiac disease.

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Additionally, some laboratory cell culture research has attempted to uncover the mechanism by which essential oils may help manage Lyme disease. They found that bandit, oregano, clove bud, geranium bourbon, and cinnamon bark were the most effective.

Finally, researchers have discovered that the treatments multiple sclerosis patients take, such as steroids, can exacerbate previous symptoms, triggering relapses.

Certain diets including keto, homeopathy, nutritional supplements, and herbal therapies have been revealed to benefit people with multiple sclerosis.

ANU’s research, published in Science Advances, was conducted in collaboration with the University of Queensland and the Francis Crick Institute.