The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries that explain how the immune system prevents itself from attacking the body’s own organs.

Their research on peripheral immune tolerance uncovered the crucial role of a special class of immune cells known as regulatory T cells. These cells act as protectors, ensuring that the immune system attacks harmful invaders while sparing the body’s own tissues.

Every day, our immune system fights off countless bacteria and viruses. But some pathogens mimic human cells to escape detection, making it vital for the body to tell the difference between foreign threats and self-tissues. The laureates’ work solved a decades-old puzzle by revealing how this self-control is maintained.

In 1995, Shimon Sakaguchi made a key breakthrough by identifying regulatory T cells, challenging the earlier belief that immune tolerance was maintained only in the thymus through the elimination of harmful cells, known as central tolerance. His work showed that the immune system had another layer of control.

Later, in 2001, Mary Brunkow and Fred Ramsdell discovered a mutation in a gene they named Foxp3 while studying mice prone to autoimmune disease. This mutation disrupted immune regulation, leading to severe illness. They later confirmed that similar mutations in humans cause IPEX syndrome, a rare but serious autoimmune disorder.

By 2003, Sakaguchi connected these discoveries, proving that the Foxp3 gene is essential for developing regulatory T cells, the same cells that prevent the immune system from attacking the body.

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