More than 30,000 Australians live with Crohn’s Disease but it is predicted this figure will rise by 20 percent in the next decade – why?
There is currently no cure for Crohn’s; patients may need medical care for a long time with regular doctor visits to monitor their condition.
In patients with Crohn’s Disease the immune system seems to overreact to substances and bacteria in the intestine, white blood cells invade the intestinal lining and produce inflammatory toxins causing chronic tissue swelling, injury and ulceration.
Dr Amanda Gavin is leading Burnet’s research program to understand how responses in our immune system can lead to the development of autoimmune diseases, like Crohn’s Disease.
“It is hard to find a solution for something if you don’t know every detail about how it works,” Dr Gavin said.
“Although immune suppression drugs can help the symptoms of Crohn’s Disease, we really need to understand the cause and effect between the immune system, intestinal tissue, and good bacteria.”
Read more about Dr Gavin’s work in the Autumn edition of IMPACT.
Crohn’s seems to occur equally in men and women, and usually appears for the first time in patients under 30 years of age.
It usually affects the lower small intestine (ileum) and the large intestine (colon), but can also target other parts of the digestive tract.
The inflammation causes abdominal pain, diarrhoea and a range of other symptoms including fever and weight loss. In severe cases, intestinal surgery may be required.
Burnet researchers using a different approach
Most of the research worldwide is focused on understanding how macrophages and other innate immune type cells handle and respond to bacteria in the gut.
“We are approaching the problem from another angle, asking instead if Crohn’s patients have altered tolerance signalling that may allow self-attacking T-cells to escape from the thymus, rather than being detained as they should be,” Dr Gavin said.
The thymus is the organ where T-cells undergo quality testing, in a process called ‘tolerance’. T-cells that show they will not attack self-antigens are released from the thymus go out to defend our bodies from microbial invaders; conversely T-cells which do attack self-antigens are normally detained in the thymus and eventually die.
Recent advances by other research groups have identified genes that are linked to Crohn’s Disease, including NOD2, a bacterial sensor protein, and IL23R, a gene that importantly keeps some T-cells alive.
Dr Gavin and her team are testing if mutations in these and other genes influence how T-cells receive self-tolerance signals in the thymus. They are also using animal models to discover if the body’s self-tolerance signals are impaired when gut bacterial load is altered.
“Gut bacteria differs from person to person and we are only now beginning to learn the effect that this bacteria can have on our entire wellbeing and immune system,” Dr Gavin said.
“Our ideal outcome would be to gain insight of how and why these tolerance mechanisms breakdown so that Crohn’s Disease and other autoimmune reactions could be prevented in the future.”