Our bodies generate a vast array of immune cells to regulate homeostasis and maintain a healthy immune system. Multiple organs and tissues help facilitate processes that preserve this balanced fitness. One particular organ that plays a critical role in health and well-being includes the thymus. The thymus is characterized as a lymphoid organ within the chest cavity that is comprised of immature immune cells. A major responsibility of the thymus includes the differentiation of T cells, which are a type of immune cell tasked with identifying and targeting foreign pathogens. Unfortunately, as we age, the thymus begins to breakdown or atrophy. This process is gradual and accelerates during puberty limiting the body’s ability to respond to new antigens or foreign pathogens. Therefore, post-pubescent individuals are more likely to become sick and need healthcare interventions as a preventative measure, such as vaccines, and medication once contracting an illness. Interestingly, as the body continues to age this nonreversible atrophy of the thymus worsens and permanently immunocompromises the individual. While it is still unclear why the thymus progressively shrinks overtime, scientists are beginning to investigate how this process occurs.
A recent article in Nature Immunology, by Dr. Jarrod Dudakov and others, define a unique feature of thymic atrophy and how it relates to aging of the immune system. Dudakov is an Associate Professor in the Translational Science and Therapeutics Division and Immunotherapy Integrated Research Center (IIRC) at Fred Hutch Cancer Center. His research focuses on how the immune system recovers from injury. He uses animal models to specifically study the thymus and generate new therapies that will enhance patient quality of life and longevity.
Dudakov and others used bioinformatic techniques, including next generation sequencing, and advanced imaging to detect changes in stem cells, which have the capacity to differentiate into various cell types. Researchers discovered two unusual changes within thymic epithelial cell (TEC) states. The TECs are age-associated and form clusters of thymic cells. Interestingly, these clusters developed into thymic tissue with no function and only got worse with age. More specifically, as the organ aged, the stem cells became less stable and loss their ability to develop and function through the downregulation of a critical protein, known as FOXN1. Dudakov and others also discovered that in an acute injury TECs expanded rapidly, further progressing irreversible thymic atrophy. Unfortunately, these age-associated TECs do not support the development of T cells, which helps explain the process of thymic dysfunction during T cell maturation.
Dudakov and his team demonstrated how the thymus atrophies with implications to the immune system. The discovery of these new cell states provides foundational knowledge to the process of thymic aging and has the potential to help develop enhanced therapies for disease. More studies and investigation could also provide the possibility to stop or slow this process down to improve overall health. Since each individual experiences thymic atrophy through aging, everyone would benefit from this type of ‘delayed’ therapy. Overall, the ground-breaking work done by Dudakov and others establishes the fundamental processes within thymic atrophy and aids in the development of enhanced treatments.