From Fighting to Healing: What the 2025 Nobel Prize Teaches Us About the Art of Resolution

When we think of the immune system, most of us picture an army: white blood cells attacking viruses, antibodies neutralizing invaders, and inflammation waging war inside the body. It’s a powerful story — and a useful one — but it’s only half the truth.

The 2025 Nobel Prize in Physiology or Medicine reminds us that defense alone is not enough. This year’s laureates — Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi — were honored for their discoveries on peripheral immune tolerance, the process that prevents our immune system from turning its weapons on ourselves. They revealed the existence of regulatory T cells (Tregs) — specialized immune “peacekeepers” that calm inflammation and guide tissues back to balance after battle.

Their work illuminates one of biology’s most elegant paradoxes: survival depends as much on knowing when to stop fighting as on knowing how to fight.

🔬 The Nobel Story: The Immune System’s Brakes

For decades, immunology was dominated by the language of attack — killer T cells, antibody responses, vaccines, and pathogen clearance. The discovery of regulatory T cells, first described by Shimon Sakaguchi in 1995, revealed a hidden half of the immune story. These cells, marked by a surface protein called CD25 and governed by a master gene named FOXP3 (discovered by Brunkow and Ramsdell in 2001), act as the immune system’s braking mechanism.

Without them, the body loses control of its own defenses. In mice and in humans, mutations in FOXP3 trigger catastrophic autoimmune disorders, where the immune system attacks the very tissues it was meant to protect.

But in healthy physiology, these same cells play a subtler, nobler role: once an infection or injury is cleared, they resolve inflammation, suppress collateral damage, and enable repair. They restore peace.

As the Nobel Assembly at Karolinska Institutet wrote, this work “laid the foundation for a new field of research and spurred the development of new treatments for cancer, autoimmune diseases, and transplantation.”

⚖️ Beyond Defense: The Era of Immune Resolution

Thirty years after Sakaguchi’s discovery, a new generation of research is redefining the therapeutic frontier. A 2024 review in Nature Reviews Drug Discovery titled “Harnessing the biology of regulatory T cells to treat disease” summarizes how scientists are learning to modulate the body’s resolution pathways — enhancing them in autoimmune diseases and damping them in cancer.

In autoimmune and inflammatory conditions, the goal is to boost regulatory T cells to restore tolerance. Experimental therapies include low-dose IL-2, nanomedicine that delivers immune-calming signals, and even cell-based therapies in which a patient’s own Tregs are expanded and reinfused to re-establish immune peace.

In cancer, the challenge flips: tumors exploit these same Treg pathways to hide from the immune system. Here, researchers are testing ways to disarm Tregs so that the immune system can regain its ability to attack.

What’s striking is that both approaches — strengthening or releasing the brakes — share the same underlying logic: health depends on balance, not extremes.

🔄 From Immune Balance to Systemic Balance

This principle extends beyond immunology. The Nobel-winning idea of peripheral tolerance can be seen as a model for the entire body’s resilience system — a balance between response, adaptation, and resolution.

In my research on Exposure-Related Malnutrition (ERM), I’ve proposed that every biological system under stress follows a similar trajectory:

1. Respond — mobilize energy and resources to confront a challenge.

2. Adapt — adjust metabolism, hormones, and structure to survive prolonged demand.

3. Resolve — restore equilibrium, rebuild reserves, and reallocate energy from defense to repair.

Just as the immune system relies on Tregs to end inflammation, the whole organism requires its own mechanisms of resolution — hormonal, metabolic, and mitochondrial — to shift from survival mode back to recovery. When this fails, the system becomes trapped in a state of chronic low-grade activation: inflammation, fatigue, muscle loss, metabolic slowdown.

In other words, ERM represents what happens when the body can respond and adapt, but cannot resolve.

⚙️ The Energy of Resolution

Resolution is not rest — it’s an active process. It requires energy, substrates, and precise coordination. In immune cells, resolution depends on ATP and NADPH, which power the anti-inflammatory and reparative reactions that follow infection. In the body as a whole, resolution demands sufficient protein, micronutrients, redox balance, and circadian alignment to fuel repair.

When energy availability is compromised — whether from chronic stress, undernutrition, toxin exposure, or mitochondrial inefficiency — the system cannot fully close the loop. Inflammatory and adaptive programs keep running, consuming fuel without restoration. The body, like an immune system without its regulatory T cells, becomes its own collateral damage.

This is why chronic fatigue, inflammation, or premature aging can emerge even without a clear “disease” — they are symptoms of unresolved adaptation.

🌱 The Shared Biology of Resilience

Seen through this lens, the 2025 Nobel discovery is not just about the immune system; it’s about the universal logic of living systems. Whether in the immune network, the endocrine axis, or the cellular stress response, resilience follows the same rhythm: activation → modulation → resolution.

True healing — biological or psychological — is not a war to be won but a cycle to be completed. The key lies in restoring the energy and signaling capacity needed for that final, often neglected phase: resolution.

This is where medicine is evolving — from suppressing symptoms to supporting recovery, from fighting disease to restoring dynamic balance.

🧩 A Universal Lesson

The immune system teaches us something profound:

Life depends on knowing not only how to respond to danger, but how to make peace afterward.

The 2025 Nobel laureates uncovered the cellular guardians of that peace. Their discoveries illuminate a path that reaches far beyond immunology — to metabolism, aging, and the very nature of resilience itself.

As we extend these insights through the ERM framework, we begin to see health not as the absence of conflict, but as the art of resolution — the graceful return to balance after every storm.

References

• The Nobel Assembly at Karolinska Institutet. Press release: The Nobel Prize in Physiology or Medicine 2025 — “for discoveries concerning peripheral immune tolerance.”

• Wardell, C. M., Boardman, D. A., & Levings, M. K. (2024). Harnessing the biology of regulatory T cells to treat disease. Nature Reviews Drug Discovery. https://doi.org/10.1038/s41573-024-01089-x

• Tippairote, T., Hoonkaew, P., Suksawang, A. et al. From adaptation to exhaustion: defining exposure-related malnutrition as a bioenergetic phenotype of aging. Biogerontology 26, 161 (2025). https://doi.org/10.1007/s10522-025-10302-2

#Regulatory T cells (Tregs), #Peripheral immune tolerance, #Resolution biology, #Autoimmunity and cancer immunotherapy, #Immune resilience and systemic recovery