Fungus-Fighting Protein Could Help Overcome Severe Autoimmune Disease and Cancer

A protein in the immune system programmed to protect the body from fungal infections is also responsible for exacerbating the severity of certain autoimmune diseases such as irritable bowel disease (IBS), type 1 diabetes, eczema and other chronic disorders, new research from The Australian National University (ANU) has found.

The discovery could pave the way for new and more effective drugs, without the nasty side effects of existing treatments.

The scientists have discovered a previously unknown function of the protein, known as DECTIN-1, which in its mutated state limits the production of T regulatory cells or so-called ‘guardian’ cells in the immune system.

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 defenses against itself.

“When this happens, the immune system wrongly perceives healthy cells as a threat, causing it to attack the body and promote the onset of autoimmune disease,” lead author Dr Cynthia Turnbull, said.

“Although the DECTIN-1 protein helps to fight fungal infections, in its mutated state it’s 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 and offers new hope to more than one million Australians who suffer from some form of autoimmune disease.”

The scientists believe they can control the immune system by turning the DECTIN-1 protein on and off, like a light switch.

“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.”

According to Dr Turnbull, this means DECTIN-1 could 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 defenses,” 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.”

Sources:

Cynthia Turnbull, Josiah Bones, Maurice Stanley, Arti Medhavy, Hao Wang, Ayla May D. Lorenzo, Jean Cappello, Somasundhari Shanmuganandam, Abhimanu Pandey, Sandali Seneviratne, Grant J Brown, Xiangpeng Meng, David Fulcher, Gaetan Burgio, Si Ming Man, Carmen de Lucas Collantes, Mercedes Gasior, Eduardo López Granados, Pilar Martin, Simon H. Jiang, Matthew C. Cook, Julia I. Ellyard, Vicki Athanasopoulos, Ben Corry, Pablo F. Canete, Carola G. Vinuesa. DECTIN-1: A modifier protein in CTLA-4 haploinsufficiency. Science Advances, 2023; 9 (49) DOI: 10.1126/sciadv.adi9566

Australian National University. “Fungus-fighting protein could help overcome severe autoimmune disease and cancer.” ScienceDaily. ScienceDaily, 6 December 2023. <www.sciencedaily.com/releases/2023/12/231206150538.htm>.

Materials provided by Australian National University. Note: Content may be edited for style and length.

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