2025 Nobel Prize in Medicine or Physiology Awarded for Key Immune System Discovery

The Nobel Assembly at the Karolinska Institute in Stockholm has awarded the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow (USA), Fred Ramsdell (USA), and Shimon Sakaguchi (Japan) “for their discoveries concerning peripheral immune tolerance.” As per the Nobel Assembly press release (NobelPrize.org), their collective research transformed understanding of how the immune system prevents autoimmune disease by identifying the key role of regulatory T cells (Tregs).

Their work uncovered how the immune system uses regulatory T cells (Tregs) to prevent harmful responses against the body’s own tissues, a mechanism essential for avoiding autoimmune disease. This groundbreaking discovery has now placed all three scientists among the 2025 Nobel Prize winners in medicine and physiology for their transformative contribution to immunology.

The Science: Peripheral Immune Tolerance and Regulatory T Cells

The immune system must distinguish between foreign pathogens and the body’s own cells. Without proper control, immune cells may attack self-tissues, causing autoimmune diseases. Earlier research showed that developing lymphocytes in the thymus undergo a process called central tolerance, where many self-reactive T cells are eliminated.

However, central tolerance is not sufficient. Some T cells that recognize self still escape deletion. The trio’s discoveries concern peripheral immune tolerance, a control mechanism in peripheral (outside the thymus) tissues to regulate or suppress self-reactive T cells.

They identified regulatory T cells, which act as the immune system’s “security guards,” monitoring and suppressing overactive immune responses.

Key developments:

• In 1995, Shimon Sakaguchi proposed that the immune system contains a distinct class of T cells that enforce peripheral tolerance and prevent autoimmune disease, challenging the dominant view that tolerance is only produced in the thymus (central).

• In 2001, Mary Brunkow and Fred Ramsdell discovered a mutation in a gene they named Foxp3 in mice with fatal autoimmune disease (scurfy mice). The gene’s counterpart in humans is also linked to an autoimmune syndrome called IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).

• In 2003, Sakaguchi showed that Foxp3 controls regulatory T cell development, thereby connecting his earlier discovery (Tregs) with the molecular mechanism identified by Brunkow and Ramsdell.

Together, these findings established a new field of immunology centered on peripheral immune tolerance, significantly deepening understanding of how the immune system maintains balance — a contribution that has since defined these scientists as 2025 Nobel Prize for Medicine and Physiology laureates.

Clinical and Therapeutic Implications

The discoveries have opened paths toward novel therapies in autoimmune disease, cancer immunotherapy, and transplantation medicine.

According to the Nobel Committee, more than 200 clinical trials are now exploring ways to manipulate regulatory T cells to modulate immune responses.

These therapeutic concepts include:

• Enhancing regulatory T cell function in patients with autoimmune diseases to suppress harmful immune responses.

• Modulating Tregs in transplant recipients to reduce graft rejection.

• Carefully suppressing regulatory T cells to boost anti-cancer immunity under controlled conditions.

While these findings have inspired over a hundred early-phase trials, most approaches remain experimental and are not yet part of standard care. For example, early clinical research at institutions such as Stanford and Osaka University is investigating regulatory T cell modulation in organ transplantation and type 1 diabetes (NobelPrize.org).

Laureates and Prize Details

• Mary E. Brunkow is senior program manager at the Institute for Systems Biology in Seattle, USA. She earned her Ph.D. from Princeton University in 1991.

• Fred Ramsdell works as a scientific adviser at Sonoma Biotherapeutics in San Francisco, USA. He holds a Ph.D. in microbiology and immunology from UCLA and earlier studied at UC San Diego.

• Shimon Sakaguchi is a distinguished professor at the Immunology Frontier Research Center of Osaka University, Japan. He holds an M.D. and Ph.D. from Kyoto University.

Each laureate receives a share of the 11 million SEK (Swedish kronor) prize (approximately US$1.2 million), plus a gold medal presented by the King of Sweden.

The Nobel Prize medicine announcement marks the first of six for 2025. The formal award ceremony will take place on December 10, the anniversary of Alfred Nobel’s death.

This year’s Nobel Prize for medicine winners continue a legacy of scientific excellence, advancing human health through discoveries that redefine our understanding of the immune system.

References:

1. Nobel Prize Press Release, nobelprize.org

2. Scientific American, “2025 Nobel Prize in Physiology or Medicine Awarded for Discoveries Key to Regulatory T Cells,” scientificamerican.com

(Rh/MSM)