by Aimee Pugh Bernard,The Conversation

Regulatory T cells suppress immune responses using a variety of molecular signals. Credit:Giwlz/Wikimedia Commons,CC BY-SA

Every day, your immune system performs a delicatebalancing act, defending you from thousands of pathogens that cause disease while sparing your body's own healthy cells. This careful equilibrium is so seamless that most people don't think about it until something goes wrong.

Autoimmune diseasessuch as Type 1 diabetes, lupus andrheumatoid arthritisare stark reminders of what happens when theimmune systemmistakes your own cells as threats it needs to attack. But how does your immune system distinguish between "self" and "nonself"?

The 2025Nobel Prize in physiology or medicinehonors three scientists—Shimon Sakaguchi,Mary BrunkowandFred Ramsdell—whose groundbreaking discoveries revealed how your immune system maintains this delicate balance. Their work on two key components of immune tolerance—regulatory T cells and the FOXP3 gene—transformed howresearchers like meunderstand the immune system, opening new doors for treatingautoimmune diseasesand cancer.

While the immune system is designed to recognize and eliminate foreign invaders such as viruses and bacteria, it must also avoid attacking the body's own tissues. This concept is calledself-tolerance.

For decades, scientists thought self-tolerance was primarily established in the parts of the body that make immune cells, such as the thymus for T cells and thebone marrowfor B cells. There, newly created immune cells that attack "self" are eliminated during development through a process calledcentral tolerance.

However, some of these self-reactive immune cells escape this process of elimination and are released into the rest of the body.Sakaguchi's 1995 discoveryof a new class of immune cells, called regulatory T cells, or Tregs, revealed another layer of protection: peripheral tolerance. These cells act as security guards of the immune system, patrolling the body and suppressing rogue immune responses that could lead to autoimmunity.

While Sakaguchi identified the cells,Brunkow and Ramsdellin 2001 uncovered the molecular key that controls them. They found that mutations in a gene called FOXP3 caused a fatal autoimmune disorder in mice. They later showed that similar mutations in humans lead to immune dysregulation and a rare and severe autoimmune disease calledIPEX syndrome, short for immunodysregulation polyendocrinopathy enteropathy X-linked syndrome. This disease results from missing or malfunctioning regulatory T cells.

In 2003, Sakaguchi confirmed thatFOXP3 is essentialfor the development of regulatory T cells. FOXP3 codes for a type of protein called atranscription factor, meaning it helps turn on the genes necessary for regulatory T cells to develop and function. Without this protein, these cells either don't form or fail to suppress harmful immune responses.

Regulatory T cells can be heroes or villains, depending on the context. When regulatory T cells don't work, it can lead to disease. Abreakdown in immune tolerancecan result in autoimmune diseases, where the immune system attacks healthy tissues. Conversely, in cancer, regulatory T cells can betoo effective in suppressing immune responsesthat might otherwise destroy tumors.

Too much or too little immune activation can lead to illness. Credit:Kevbonham/Wikimedia Commons,CC BY-SA

Understanding how FOXP3 and regulatory T cells work launched anew era in immunotherapiesthat harness the immune system to treat autoimmune diseases and cancer. For autoimmune diseases such asrheumatoid arthritisandType 1 diabetes, researchers are exploring ways to boost the function of Tregs.For cancer, the goal is to inhibit Tregs, allowing the immune system to target tumors more aggressively.

Beyond disease treatment, this research may alsoimprove organ transplantation, where immune tolerance is crucial to prevent rejection. Scientists are exploring how to engineer or expand Tregs to help the body accept transplanted tissues over the long term.

Continuing to unlock the secrets of immune regulation can help lead to a future where the immune system can beprecisely tuned like a thermostat—whether to turn it down in autoimmunity or rev it up against cancer.

The 2025 Nobel Prize reminds us that science, at its best, doesn't just explain the world—it changes lives.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginal article.

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