Most of us don’t give any thought to our thymus even though the gland, which is located behind the breast bone, plays a crucial role in our health.
“I call it the most important organ you’ve never heard of,” says researcher Daniel Gray, of Australia’s Walter and Eliza Hall Institute (WEHI). “People aren’t aware of it or they confuse it with other glands like the thyroid or thalamus.”
The thymus is a key part of our immune system. It is the only organ in the body that can make T-cells, which are powerful fighters of disease and infection. Production of these white blood cells kicks off when we’re still in the womb and continues through childhood. When we hit puberty, however, the thymus starts shrinking.
“The number of new T-cells produced in the body declines after puberty, irrespective of how fit you are,” says Gray. “By age 65, the thymus has virtually retired. This weakening of the thymus makes it harder for the body to deal with new infections and cancers. We think it’s an important piece of that puzzle of why immunity wanes with age.”
There is debate around exactly why the thymus goes into such a dramatic decline. One theory is that it reduces the risk of developing autoimmune conditions such as type 1 diabetes or multiple sclerosis later in life. Another that it helps prevent a type of leukaemia that is caused by the out-of-control growth of T-cells.
For most people, the shrinking thymus is a normal part of the ageing process and not something to lose sleep about.
“But there are situations where lacking thymus function is a major problem, such as when people receive heavy chemotherapy or other treatments for cancer,” says Gray. “They are able to restore most of their immune system, but if the thymus is atrophied and it’s not working properly any more, they don’t get back their T-cells and that leaves them vulnerable to infection.”
Efforts are underway to understand more about the biological processes behind the decline of the thymus in the hope of finding ways to restore immunity for these vulnerable patients.
Using advanced imaging, a research team at the institute has now identified two new cell types that cause the thymus to lose its function. These cells, which appeared only in the defective thymus of older mice and humans, were found to form clusters around T-cell growth areas and create scars. “So, not only is it shrinking but there’s this scarring that’s occurring inside the tissue and preventing it from making T-cells properly and regenerating,” Gray says.
The function of the thymus was discovered in 1958 by Jacques Miller, now an emeritus professor at the institute. He was researching leukaemia in the UK when he identified that the thymus was a crucial part of the immune system.
“He found that when you take the thymus away from very young mice, they become susceptible to disease, and also that they could then accept skin grafts from other mice,” says Gray.
Building on his work, Gray says the next step will be to understand more about these new cell types. “We want to know, in molecular detail, how they come to be and what makes them different from the cells that are functioning normally, because that will inform ways that we can use drugs to try to reverse or remove this scarring feature.”
It remains to be seen whether immunity can be restored in older animals by preventing the decline of the thymus without upping the risk of autoimmunity or leukaemia. But it may be possible to develop a restorative therapy for patients who are recovering from medical treatments, such as chemotherapy, which will help replenish their T-cells and strengthen their immune system.
“If it turned out to have a very safe profile then you might consider trialling it for something like Covid, where, for a variety of reasons, older people are not as good at responding to this new infection,” says Gray.
The immune system is tremendously complex. Like the brain, it has the ability to learn and remember as it tailors its response to all kinds of different things. The thymus plays a key role in this. “We know from previous studies that, even as adults, we have the capacity for the thymus to regenerate,” says Gray.
“This has led to international efforts to find strategies to restore thymus function. I think discoveries like ours are getting us closer to realising whether this would be a useful treatment.”
