Regenerating the Thymus

The thymus plays a vital role in the maintenance of a healthy immune system, producing T cells which provide defence against viruses and bacteria and help with cancer surveillance. The ability of the thymus to regenerate itself after damage caused by infection, chemotherapy or radiation is critical for preventing T cell deficiency and associated conditions. “It’s really important to have a healthy thymus to not only be able to respond to new infections, but also for clearing cancer malignancies,” said Dr Jarrod Dudakov, Assistant Member in the Program of Immunology at Fred Hutchinson Cancer Research Center in a recent interview.

While it is clinically well known that the young thymus can rebound after such damage, not much was known about the underlying process, and why this ability declines with age.

A new Science Immunology paper has demonstrated that endothelial cells (EC) in the thymus are responsible for organising the regeneration process. In response to damage, the ECs produce growth factor proteins called BMP4, which stimulate epithelial cells to regrow.

In mice, the researchers were able to show that blocking BMP4 reduced thymic repair in response to non-lethal radiation, whilst the administration of ECs to the thymus boosted regeneration.

The findings could pave the way to developing new treatments to restore thymic function, in response to both damage and ageing. “First of all, we can now see whether we can take this special effector, BMP4, and maybe develop it as a drug that could be given to patients dealing with a damaged thymus, or in older people or cancer patients, to enhance immune function in response to a flu vaccine, for instance,” said Dr Marcel van den Brink, Head of the Division of Hematologic Oncology at Memorial Sloan Kettering Cancer Center in a recent interview.