Nobel Prize in Physiology or Medicine Awarded to Specially Appointed Professor Sakaguchi of the University of Osaka and two American researchers for discovery of regulatory T Cells

On the 6th, the Karolinska Institute in Sweden announced that the 2025 Nobel Prize in Physiology or Medicine will be awarded to Shimon Sakaguchi, Specially Appointed Professor at the Immunology Frontier Research Center of the University of Osaka (74), Dr. Mary E. Brunkow of the Institute for Systems Biology in the United States, and Dr. Fred Ramsdell of Sonoma Biotherapeutics in the United States, for their discovery of regulatory T cells. The work of the immune system through regulatory T cells is expected to contribute to cancer treatment and the treatment of autoimmune diseases. Professor Sakaguchi is the sixth Japanese recipient of the Nobel Prize in Physiology or Medicine and the latest since Dr. Tasuku Honjo in 2018.

Our bodies prevent the invasion of many microorganisms daily through the function of the immune system. However, it was not understood how the immune system determines what to attack and what to protect. The function of regulatory T cells discovered by Sakaguchi and others is to control immunity as "guards of the immune system."

In the human body, there are T cells, immune cells that have the function of detecting microorganisms and alerting other immune cells. In the 1980s, it was believed that the immune system eliminates harmful immune cells that recognize self-antigens as foreign substances through a mechanism called central immune tolerance in the thymus. However, in 1995, Sakaguchi demonstrated through experiments that when T cells cultured from other mice were injected into mice whose thymus had been removed, autoimmune diseases did not develop, discovering that there were immune systems beyond those previously considered.

Meanwhile, in 2001, Brunkow and Ramsdell discovered that mice inheriting specific gene lineages had high rates of autoimmune diseases. When they investigated in detail through whole genome analysis, they found that there was a mutation in a gene called Foxp3. This gene mutation was found to cause a hereditary syndrome called IPEX syndrome in humans as well.

Then, Sakaguchi discovered that this Foxp3 gene controlled the development of regulatory T cells. It was also understood that regulatory T cells, after eliminating foreign substances, would settle down to prevent runaway reactions in a series of processes.

The Karolinska Institute praised them "for their discoveries concerning peripheral immune tolerance, how the immune system is kept in check, and spurring the development of medical treatments for cancer and autoimmune diseases." This is expected to lead to the establishment of treatment methods for cancer immunotherapy and rejection reactions in organ transplantation.

There are two types of T cells: those that trigger immune responses and those that suppress immune reactions. When immune responses are strong, autoimmune diseases and allergies occur, and when immune reactions are suppressed, cancer develops. Until this discovery, it was difficult to distinguish between the two. With the balance being clarified, pathways for treatment were opened. Based on these achievements, a company called "RegCell" was established in 2016 using the English name for regulatory T cells, and Sakaguchi has been engaged in drug development as a member.

At a press conference held on the 6th at the University of Osaka's Suita Campus, Sakaguchi said, "I feel greatly honored. I am indebted to the students and collaborative researchers. I am also grateful to those people. COVID and vaccines have become topics of discussion, but two things are important: how to strengthen immune responses and how to suppress abnormal responses. I have been researching how to negatively regulate. This research will lead us to how to treat rheumatoid arthritis and type 1 diabetes, and how to prevent them from occurring."

During the press conference, he received a telephone call from Prime Minister Shigeru Ishiba, who offered words of praise, saying, "Congratulations. This is splendid research that we can boast of to the world. Your 40 years of research have led to today."

The prize money of 11 million Swedish kronor (approximately 175 million yen) will be divided equally among the three laureates. The award ceremony will be held in Stockholm, Sweden on December 10.