A new study has discovered why a key immune organ, the thymus, declines with age. The findings could help scientists boost ageing or depleted immune systems one day.
Located behind the sternum, the thymus is the only organ in the body capable of developing T cells.
These are a type of immune cell that plays a critical role in detecting and responding to pathogens, such as viruses and bacteria, and in getting rid of infected, defective, or cancerous cells.
But the thymus doesn’t pump out a steady supply of T cells throughout our lifetime. Instead, it shrinks with age and T cell producing areas become replaced with fatty tissues.
“The number of new T cells produced in the body significantly declines after puberty, irrespective of how fit you are. By age 65, the thymus has virtually retired,” says Professor Daniel Gray, laboratory head at WEHI in Australia and co-author on the study in Nature Immunology.
“This weakening of the thymus makes it harder for the body to deal with new infections, cancers and regulate immunity as we age.
“This is also why adults who have depleted immune systems, for example due to cancer treatment or stem cell transplants, take much longer than children to recover.
“These adults need years to recover their T cells – or sometimes never do – putting them at higher risk of contracting potentially life-threatening infections for the rest of their lives.
“Exploring ways to restore thymic function is critical to finding new therapies that can improve outcomes for these vulnerable patients and find a way to ensure a healthy level of T cells are produced throughout our lives.
“Our discovery provides a new angle for thymic regeneration and immune restoration, could unravel a way to boost immune function in vulnerable patients in the future.”
The researchers found 2 previously unknown states of a type of specialised cell in the thymus’ outer layer (epithelium).
These atypical thymic epithelial cell states appeared only in the defective thymus of older mice and humans, where they form clusters around and impair T cell growth areas.
These regions expand after the thymus experiences damage to form ‘scars’ that prevent it from regenerating.
“While a large focus of research into thymic loss of function has focused on the shrinking process, we’ve proven that changes that occur inside the organ also impact its ability to function with age,” says co-author Dr Kelin Zhao of WEHI.
“By capturing these cell clusters in the act and showing how they contribute to loss of thymic function, we’ve been able to do something no one else has ever done before, largely thanks to the incredible advanced imaging platforms we have at WEHI.
“This knowledge enables us to investigate whether these cells can be therapeutically targeted in future, to help turn back the clock on the ageing thymus and boost T cell function in humans as we get older. This is the goal our team is working towards.”
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