The thymus is one of those organs whose name is little known, but it plays a crucial role in keeping our immune system healthy. But like all organs, the thymus, located in the upper chest, becomes less efficient with age. It's difficult to restore the thymus once it has begun to deteriorate, but future treatments may take inspiration from an unexpected source: the axolotl.
New research published in Science Immunology discovered that axolotls, eccentric amphibians that often have a pink hue, can regenerate their thymus after it is removed from the body. This regenerative capacity, observed specifically in young axolotls, may now serve as the basis for treatment options aimed at achieving more effective thymic regrowth.
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Training immune cells to fight
Tracking thymus growth in an axolotl.
(Image courtesy of Maximina Laboratory)
The thymus is an integral part of the lymphatic system, which clears fluid between tissues and sends immune cells to fight infections.
Many may find it easier to recognize secondary lymphoid organs such as lymph nodes — which filter foreign substances from the lymph, the watery fluid that flows throughout the body — and the spleen, which filters the blood and removes old or damaged red blood cells.
On the other hand, the thymus is one of the main lymphoid organs. Its main function is training T cellswhich are mature white blood cells (or lymphocytes) that fight disease and infection. In other words, the thymus is like an immune response coach, training T cells by exposing them to proteins they shouldn't attack as they go on missions throughout the body.
However, already in the first year after birth, the thymus begins to shrink – this process is called involution. Involution of the thymus accelerates after puberty as the organ is replaced by fatty tissue, and by age 65, the production of new T cells virtually stops. This leads to a weakened immune system in old age, increasing the risk of infections, immune disorders and cancer, according to the Walter and Eliza Hall Institute for Medical Research.
Axolotl superpower
Scientists have looked for ways to restore the thymus through cell therapy or bioengineering, but these strategies only delay the involution of the thymus rather than completely regenerate it.
Complete thymic regeneration was not previously known to exist in any vertebrates, although scientists have speculated that salamanders may have a better chance – they are the only land vertebrates that can grow back whole limbs.
To explore the possibility of complete thymus regeneration, researchers involved in the new study turned to axolotlsalamanders that retain their “tadpole” shape and live underwater their entire lives.
The researchers surgically removed the thymus gland from young axolotls and then observed how the organ could regenerate. They found that within 35 days of surgery, about 60 percent of the axolotls had regenerated thymic nodules. The most important aspect is that this was de novo regeneration – from scratch, and not using remnants of the missing thymus.
A step towards thymus regeneration
The regenerated axolotl thymuses were eventually able to recruit cells that matured into T cells, just as the original thymuses would have done.
The researchers also wanted to know what promotes de novo thymic regeneration at the molecular level. They first studied Foxn1, a regulatory gene involved in thymus development. According to statement According to the study, genetic deletion of Foxn1 did not prevent thymic regeneration, but resulted in the development of smaller thymic tissues than the natural version of the gene in axolotls.
Growth factor midkine (MDK), a protein that is highly expressed during human embryonic development, may instead be a key factor. The researchers found that MDK expression increased in axolotls after thymus removal, and MDK inhibition decreased regeneration.
The researchers say further research into the molecular pathways underlying thymic regeneration may help identify treatments that improve thymic function in elderly or immunocompromised patients.
Read more: What is regeneration and can other organs like the liver regenerate?
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