2025 Nobel Prize of Physiology: The Immune System’s Brakes

The immune system is like an invisible army that patrols the body day and night, always ready to identify and neutralize any invader — from sneaky viruses to opportunistic bacteria. More than just a defense mechanism, it’s an intelligent network capable of learning, remembering, and distinguishing what belongs to the body from what poses a threat. This delicate dance between attack and tolerance, essential to maintaining health, takes center stage in the discoveries honored with the 2025 Nobel Prize in Physiology or Medicine, which reveal that the key to successful immunity lies not only in knowing when to fight — but also in knowing when to stop.

What Is the Immune System?

It is, essentially, a recognition system that distinguishes what belongs to the body from what is foreign. The evolutionary advantage of such a system is enormous, and some form of it has existed since the earliest animals appeared on Earth — after all, parasitic microorganisms had been around long before the first of them started crawling.

This remarkable system, taking us mammals as a reference, is divided into two main parts: innate and adaptive defenses, which together protect the body from pathogens that see us as a source of food.

The first part consists of everything that is always running at full speed, providing broad protection. This includes the barriers of our skin and the mucosal linings of the nose and mouth, for instance, as well as immune cells that patrol the body, searching for characteristic molecular signatures of viruses, bacteria, and fungi. These make up our first line of defense and have been with us since the moment we were born.

The second part is even more fascinating, though slower to respond when infection strikes. It is a highly specific defense that involves cells known as lymphocytes (a specialized type of white blood cell) and antibodies. This defense is possible because our bodies contain an almost infinite diversity of lymphocytes, each equipped with uniquely made receptors — ensuring that there is always at least one capable of recognizing any given pathogen, provided it is activated in time. But, of course, not everything runs smoothly all the time.

Autoimmune Diseases

Our immune systems must be extremely precise in distinguishing friend from foe. Normally, a remarkably clever mechanism “trains” lymphocytes to recognize as enemies only particles that are not part of our own body — a process known as immunological tolerance.

In simple terms, this involves exposing immature T cells — inside an organ called the thymus (located just behind the sternum) — to proteins representing the body’s own tissues. If a T cell reacts to one of these self-proteins, it is eliminated before it can mature. This process prevents self-reactive lymphocytes from attacking the body.

However, because no biological system is perfect, some rebellious cells occasionally escape this elimination process, sometimes due to inherited mutations that impair proper detection of defects. For example, in type 1 diabetes, during childhood, the immune system gradually destroys the pancreatic beta cells, which produce insulin, until the body becomes entirely dependent on external sources of the hormone.

The discovery celebrated at this year’s Nobel Prize

But how does the body deal with those few rogue cells that escape control? That question lies at the heart of the discovery honored with the 2025 Nobel Prize in Physiology or Medicine.

Shimon Sakaguchi, from Osaka University in Japan, discovered a new type of T cell associated with the improvement of autoimmune conditions. In the 1990s, Sakaguchi observed that when the thymus was removed from newborn mice, their immune systems began to attack their own tissues. However, when T cells from healthy donors with intact thymuses were transferred into them, the autoimmune symptoms disappeared.

Through these experiments, he identified a new subgroup of T lymphocytes that, in addition to expressing the CD4 receptor (typical of helper T cells), also displayed CD25. These cells — later known as regulatory T cells (Tregs) — were responsible for suppressing excessive immune responses and maintaining tolerance to self. They act by damping down the activity of other lymphocytes, essentially “calming” the immune response to prevent damage to the body.

A few years later, Mary E. Brunkow and Frederick J. Ramsdell, working at a biotechnology company focused on developing treatments for autoimmune diseases, identified a gene essential for the development of these same cells — Foxp3.

Brunkow contributed most to the genetic work, cloning and identifying the relevant mutations, while Ramsdell’s team focused on the biological function of the gene. Ultimately, the combined efforts of these three scientists provided the scientific community with tools to isolate and study regulatory T cells in detail, sparking an explosion of research in the field.Today, countless therapeutic strategies are being developed based on these discoveries.

What Comes Next?

This discovery holds great potential for developing effective treatments for autoimmune diseases — and even certain cancers, since tumors can recruit regulatory T cells to hide from immune surveillance. Tregs may also help improve organ transplantation outcomes, reducing the risk of graft rejection.

This story also highlights that a deep understanding of science opens the door to careers at the forefront of discovery — where curiosity directly translates into technologies that benefit humanity.

The work honored by this year’s Nobel Prize was carried out mostly in the late 1990s. It took nearly 30 years for this achievement to be recognized — a testament to the importance of patience, perseverance, and open-mindedness for anyone striving to do excellent work in any field, but especially in science.

As Mary Brunkow reflected, the team knew they were doing something important, but no one was thinking in terms of a Nobel Prize — they were focused on translating their findings into innovations that could transform people’s lives.

Etapa SigmaCamp: where knowledge comes alive and the future of science begins

The STEM summer camps, such as the Etapa SigmaCamp, function as true laboratories of scientific inspiration. By bringing together young talents in a dynamic, collaborative, and intellectually stimulating environment, these programs awaken a genuine interest in investigation, logical reasoning, and applied experimentation. More than just learning from renowned scientists and educators, participants experience the real process of discovery — formulating hypotheses, testing ideas, analyzing results, and developing creative solutions for concrete challenges.

In every edition, we have semilabs, lectures, and other activities for different areas of science, including biology. In the 2024 edition, we had a workshop called "What is in your blood," led by Professor Elena Yakubovskaya from Stony Brook University, where students were able to collect blood samples, mix them with antibodies, and identify their blood type and Rh factor.

Experiences like this go far beyond academic content: they promote the development of creativity, self-confidence, and a vision for the future. It is in this fertile setting that the next names in science emerge, capable of transforming the world with innovation and knowledge — as Sakaguchi, Brunkow, and Ramsdell did in their time.

Happy studying!