Every day, your immune system performs a delicate balancing 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 diseases such as Type 1 diabetes, lupus and rheumatoid arthritis are stark reminders of what happens when the immune system mistakes your own cells as threats it needs to attack. But how does your immune system distinguish between “self” and “nonself”?
The 2025 Nobel Prize in physiology or medicine honors three scientists – Shimon Sakaguchi, Mary Brunkow and Fred 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 how researchers like me understand the immune system, opening new doors for treating autoimmune diseases and cancer. The 2025 Nobel Prize in physiology or medicine was awarded to Shimon Sakaguchi, Mary Brunkow and Fred Ramsdell.
How immune tolerance works
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 called self-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 the bone marrow for B cells. There, newly created immune cells that attack “self” are eliminated during development through a process called central 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 discovery of 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 Ramsdell in 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 called IPEX syndrome, short for immunodysregulation polyendocrinopathy enteropathy X-linked syndrome. This disease results from missing or malfunctioning regulatory T cells.
In 2003, Sakaguchi confirmed that FOXP3 is essential for the development of regulatory T cells. FOXP3 codes for a type of protein called a transcription 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.
Harnessing the immune system for medicine
Regulatory T cells can be heroes or villains, depending on the context. When regulatory T cells don’t work, it can lead to disease. A breakdown in immune tolerance can result in autoimmune diseases, where the immune system attacks healthy tissues. Conversely, in cancer, regulatory T cells can be too effective in suppressing immune responses that might otherwise destroy tumors.
Understanding how FOXP3 and regulatory T cells work launched a new era in immunotherapies that harness the immune system to treat autoimmune diseases and cancer. For autoimmune diseases such as rheumatoid arthritis and Type 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 also improve 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 be precisely 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.
- Cancer
- Autoimmune diseases
- Immune system
- Immunology
- Nobel Prize
- T cells
- Immune cells
- Immunotherapy
- Immune response
- Immune tolerance
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Major rifts over key health care issues are at the heart of the federal government shutdown that began at the stroke of midnight on Oct. 1, 2025.
This is not the first time political arguments over health care policy have instigated a government shutdown. In 2013, for example, the government shut down due to disputes over the Affordable Care Act.
This time around, the ACA continues to play a central role, with Democrats demanding, among other things, an extension of subsidies for ACA plan insurance premiums that are set to expire at the end of 2025. Democrats are also holding out to roll back cuts to the Medicaid program that President Donald Trump signed into law on July 4, as part of what he called his “One Big Beautiful Bill.”
Without a budget agreement in place, Trump ordered most federal agencies to wind down their nonessential activities. The shutdown will continue until Congress passes either a short-term or long-term funding bill and Trump signs it.
Government shutdowns are nothing new, but as a health policy expert, I worry this time around the impasse may have far-reaching effects on health care.
Even as Democrats stage their battle over access to health care, the shutdown itself could also make it harder for Americans to get the care they need. Meanwhile, Trump has threatened to use the crisis to permanently cut federal jobs on a mass scale, including ones in the health care sector, which could substantially reshape federal health agencies and their ability to protect Americans’ health.
The partisan health care divide
Historically, questions about how the government should support access to health care have long been a source of conflict between the two main political parties. The passage of the ACA in 2010 and its implementation have only intensified this friction.
In the lead-up to the current shutdown, Republicans needed Democratic votes in the Senate to pass a bill that would keep funding the government at existing levels at least until November.
In return for their support, Democrats sought several concessions. A major one was to extend subsidies for ACA insurance policy premiums, which were established during the COVID-19 pandemic. These subsidies addressed a shortcoming in the ACA by decreasing premiums for millions of Americans – and they played a crucial role in more than doubling enrollment in the ACA marketplaces.
Without this extension, ACA premiums are set to rise by more than 75% in 2026, and the Congressional Budget Office estimated that 4.2 million Americans would lose insurance. At least some Republicans seemed open to considering the ACA subsidies, particularly those from districts that were more moderate and that had large numbers of people enrolled in ACA plans. But many have objected to doing that as part of the budget process.
Democrats are also pushing to renegotiate some of the changes made to Medicaid in the budget bill. These include new work requirements that are a cornerstone of Republican demands, under which certain adults would have to work or engage in qualifying activities to maintain Medicaid benefits. Work requirements are set to take effect in 2027, but implementing them would lead to an estimated 5 million people losing their health insurance coverage. ACA subsidies are a major bone of contention in the standoff between Democrats and Republicans.
Most contentiously, these rollbacks to Medicaid cuts would reverse restrictions that made immigrants who are generally present in the country legally, such as refugees and asylum-seekers, ineligible for Medicaid and ACA coverage. These restrictions, which were included in the budget bill, could lead to the loss of insurance for about 1.4 million lawfully present immigrants, the Congressional Budget Office has estimated.
Republicans have balked at these demands, taking particular issue with the prospect of restoring Medicaid benefits to immigrants. Some Republicans – and Trump himself – have misconstrued the Democrats’ position, saying they are seeking free health care for immigrants in the country illegally.
What kinds of health services might be affected?
Most obviously, large-scale staff reductions would interfere with a wide range of health-related services not considered essential during the shutdown. This includes everything from surveying and certifying nursing homes to assisting Medicaid and Medicare beneficiaries and overseeing contracts or extra payments to rural ambulance providers.
Some seniors may face an immediate impact as two programs have now lost funding without a new budget in place. One expanded access for seniors to telehealth services. The other allowed people to receive services at home that are generally provided in a hospital.
Crucially, most seniors will continue to receive Social Security payments. However, providers might be hesitant to schedule patients covered by Medicare if the shutdown drags on over a long period of time. This is because payments to medical providers would likely be delayed.
What health services will continue to function?
The Centers for Medicare and Medicaid Services has indicated that there is enough funding for Medicaid, the government program that primarily provides health services to low-income Americans, to support the program through the end of the calendar year. If the shutdown lasts beyond that, states may have to decide whether to temporarily fund the program on their own or whether to reduce or delay provider payments. However, no previous shutdown has ever lasted more than 34 days.
Community health centers are generally expected to receive some funding, at least for now. These providers offer nonemergency medical services for about 34 million Americans each year. Many also provide important services across the nation’s schools. However, if the standoff continues for more than a few days, those centers may struggle to keep their doors open.
Health and Human Services has also indicated that it will use all available funding to maintain “minimal readiness for all hazards” and will maintain certain medical services, such as the Indian Health Service. The Veterans Health Administration will also stay open. One of the agencies most affected by previous layoffs, the Food and Drug Administration, has indicated that it would be exempt from further cuts.
A longer-term view
Ultimately, the severity of the shutdown’s effects on health care will depend on how long it lasts.
It will also depend on whether Trump makes good on his stated intention to use the shutdown as “an unprecedented opportunity” to reshape the federal bureaucracy. The White House announced plans for potential mass firings of workers, particularly those at “Democrat Agencies.”
Whether this threat is simply a bargaining tactic remains to be seen, and it’s unclear whether health-related workers and agencies are in the crosshairs. But given that previous layoffs specifically targeted health programs, more permanent reductions in programs that affect health care may be on the way.
https://theconversation.com/how-does-your-immune-system-stay-balanced-a-nobel-prize-winning-answer-266842
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