Stockholm, Sweden: The Nobel Assembly at Karolinska Institutet announced on October 6, 2025, that the Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow (Institute for Systems Biology, Seattle, USA), Fred Ramsdell (Sonoma Biotherapeutics, San Francisco, USA), and Shimon Sakaguchi (Osaka University, Japan) for their pioneering work on peripheral immune tolerance.

The laureates have been recognised “for their discoveries concerning peripheral immune tolerance”, which illuminate how the immune system is regulated to prevent it from attacking the body’s own tissues. Their research has had a transformative impact on our understanding of autoimmune diseases, cancer immunotherapy, and organ transplantation.

Understanding peripheral immune tolerance

The human immune system protects the body from thousands of invading microbes daily. However, many pathogens mimic human cells, creating a challenge for the immune system to distinguish self from non-self. Errors in this process can trigger autoimmune diseases, where the immune system attacks the body itself.

The Nobel laureates identified the immune system’s security guards—a special class of cells known as regulatory T cells (Tregs). These cells monitor other immune cells, ensuring that the immune system tolerates the body’s own tissues while still defending against pathogens.

Olle Kämpe, chair of the Nobel Committee, stated, “Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases.”

Key discoveries

Shimon Sakaguchi first made a breakthrough in 1995, identifying a previously unknown class of immune cells that protect the body from autoimmune reactions. This challenged the prevailing view that immune tolerance occurred only in the thymus, through central tolerance, where harmful immune cells are eliminated.

In 2001, Mary Brunkow and Fred Ramsdell made a complementary discovery. Studying a specific mouse strain prone to autoimmune diseases, they identified a mutation in the Foxp3 gene. They demonstrated that mutations in the human equivalent of this gene cause IPEX, a severe autoimmune disorder.

Two years later, Sakaguchi linked these findings by showing that the Foxp3 gene governs the development of regulatory T cells, confirming their essential role in peripheral immune tolerance.

Impact on medicine

The discovery of regulatory T cells and their genetic regulation has launched the field of peripheral tolerance, opening new avenues for medical research and therapy. It has significant implications for:

  • Autoimmune diseases: Understanding Tregs helps design therapies to suppress inappropriate immune responses.
  • Cancer treatment: Modulating Tregs can enhance immune attacks against tumors.
  • Organ transplantation: Improved tolerance can reduce rejection risks, increasing the success of transplants.

Several treatments based on these discoveries are already undergoing clinical trials, demonstrating the practical and transformative impact of this research.

Conclusion

The awarding of the 2025 Nobel Prize in Physiology or Medicine to Shimon Sakaguchi,Mary Brunkow and Fred Ramsdell recognises decades of work that has fundamentally changed our understanding of the immune system. By uncovering how regulatory T cells prevent the body from attacking itself, the laureates have paved the way for novel treatments for autoimmune diseases, cancer, and transplantation, marking a major milestone in modern medicine.