¡ò TechnologyJournalist Liu Xia

The strong immune system of the human body needs precise regulation, otherwise it may attack our own organs. Mary E. Brunkow of the US Institute of System Biology, Fred Ramsdell of Sonoma Biotherapy, and Shimon Sakaguchi of the University of Osaka, Japan, have jointly won the Nobel Prize in Physiology or Medicine in 2025 for their breakthrough discovery in the mechanism of ¡°external immune tolerance¡±. Their research reveals the deepest mysteries of how the immune system can avoid attacking its own tissues and protect human health.

Every day, our bodies face the invasion of thousands of microbes, and the immune system is the loyal guardian of these invasions. However, some pathogens vary in shape and can even disguise into the "shape" of human cells to avoid the attack of the immune system.

The three scientists¡¯ answers point to the ¡°mediators¡± in the human body ¨C regulatory T cells. It can suppress overactive immune responses and prevent immune cells from attacking their own tissues.

¡°Their findings have radically changed our understanding of the mechanisms that the immune system works, explaining why most people don¡¯t develop serious autoimmune diseases,¡± said O¡¯Leary Carper, chairman of the Nobel Committee.

Regulatory T cell working art diagram

In 1995, Shifumi Sakaguchi's research challenged the academic consensus. At that time, the scientific community generally believed that immune tolerance mainly relied on the process of "central tolerance" to remove immune cells in the thymus that might attack its own tissues. However, Shifumi Sakaguchi found that even after the central tolerance process, some potentially aggressive T cells will still enter peripheral tissues.

For the first time, he identified a subset of T cells with immunosuppressive functions-regulatory T cells. They monitor other immune cells and ensure that the immune system tolerates its own tissues, thereby protecting against autoimmune diseases. This discovery laid the foundation for the theory of "peripheral immune tolerance".

The time came in 2001, when Branco and Ramsdale studied a mouse model of a susceptible multi-organ autoimmune disease and discovered its cause was a mutation in the key gene Foxp3. Further studies showed that the corresponding gene mutation in the human body could lead to a rare and deadly genetic autoimmune disorder, namely immunodeficiency, polynomial disorder, intestinal accompanied X chromosome chain syndrome. The disease causes regulatory T-cell function defects, thereby triggering severe autoimmune responses, accumulating many organs such as the intestines, endocrine glands and skin.

Branco and Ramsdale discovered the mutant gene Foxp3 in scurfy mice

Two years later,Ûà¿ÚÖ¾ÎÄ linked these two important findings to prove that Foxp3 is the control gene that regulates the development and function of T cells. Mice with a lack of Foxp3 were unable to produce functional regulatory T cells, and the overall autoimmune response quickly emerged. This correlation study not only established the molecular basis of regulatory T cells, but also marked the field's entry into the phase of functional and mechanical system analysis.

Nowadays, regulatory T cells have been recognized as the core regulators of immune homeostasis. Like a "patrol team" in the body, they continuously monitor the activity of other immune cells to ensure an accurate and moderate immune response and avoid accidental injury to normal tissues.

How harmful T cells are eliminated

The research of the three winners has not only paved the way for the important field of "extraterrestrial immune tolerance", but also promoted the treatment of cancer and autoimmune diseases. Treatments based on regulatory T cells are being actively explored for the treatment of autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and are also expected to give rise to more successful organ transplant surgery.

From basic science to clinical transformation, the research of Branco, Ramsdale and Sakamoto Zhivun gradually accurately uncovered the mystery of the human body inining a fine balance between defending external enemies andining self-health, and wrote an important chapter for the care of human health.

Source: Science and Technology Daily The pictures in the article are all from the Nobel Prize official website