Nobel prize- peripheral tolerance
The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries on peripheral immune tolerance.
Have you ever wondered why our immune system attacks harmful pathogens or other foreign substances and avoids attacking our own cells?
This is made possible by a remarkable balance that is maintained through a mechanism known as self-tolerance. The majority of immune cells are produced in the thymus and bone marrow. The self-reactive immune cells are destroyed by a mechanism called central tolerance. However, some of the potentially reactive cells escape into the body. These cells are made inactive or eliminated by another mechanism known as peripheral tolerance.
Peripheral tolerance
The self-reactive immune cells that escape into the body are regulated by a set of immune cells known as T regulatory cells (Tregs). The T regulatory cells were discovered by Sakaguchi in 1995. The discovery of a molecular key or the gene that controls the T regulatory cells, FOXP3, by Brunkow and Ramsdell in 2001 was groundbreaking. In 2003, Sakaguchi confirmed that FOXP3 is essential for the development of T regulatory cells.
Understanding these mechanisms has greatly helped doctors in treating various autoimmune diseases and certain types of cancer. Interestingly, Tregs can act as both heroes and villains, depending on the circumstances.
Conditions affected by the defect in the immune tolerance
-
Autoimmune diseases - a breakdown in immune tolerance can result in autoimmune conditions such as rheumatoid arthritis, diabetes, and lupus.
-
Cancer- the overactivity in immune tolerance can lead to immune suppression, which can progress to cancer.
Significance of the discovery
The discovery of Tregs and FOXP3 has revolutionised our understanding of the immune system, leading to the development of immunotherapies that aid in the treatment of various autoimmune diseases and cancers. Ongoing research in organ transplantation, where the immune system plays a crucial role, is helping improve graft acceptance and transplant success.
The discovery of Tregs and FOXP3 has opened new avenues in medical research. Further discoveries may lead to fine-tuning the immune system by upregulating it or downregulating it.
Share your thoughts about the discovery!
MBH/PS