2025 Nobel Prize: regulatory T cells — how to stop the immune system from attacking its own cells and what it means for MS

June 3, 2026

Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi won the 2025 Nobel Prize in Physiology or Medicine for discoveries on peripheral immune tolerance — regulatory T cells (Tregs) and the FOXP3 gene. Here is what it concretely means for multiple sclerosis and millions of people with autoimmune disease.

What happened

Readers ask me about this often, so I have put the practical points together in one place. On 6 October 2025 the Karolinska Institute in Stockholm announced that the Nobel Prize in Physiology or Medicine had been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi for their discoveries explaining peripheral immune tolerance — that is, how the body keeps its own immune system from attacking its own cells ([NobelPrize.org — Press release 2025](https://www.nobelprize.org/prizes/medicine/2025/press-release/)). The discovery centres on regulatory T cells (Tregs) and the FOXP3 gene that controls them. Without Tregs, the immune system behaves like an army with no command — it attacks everything, including the myelin in your own brain and spinal cord. That is exactly what happens in multiple sclerosis.

How they got there

Shimon Sakaguchi (Osaka, Japan) in 1995, against the prevailing dogma, described a special subset of T cells that quieten down other immune cells rather than activating them. Immunology at the time believed autoimmunity was prevented only in the thymus — Sakaguchi proved there is a second, "peripheral" line of defence ([Sakaguchi 1995, J Immunol](https://pubmed.ncbi.nlm.nih.gov/7636184/)).

Mary Brunkow and Fred Ramsdell (Seattle, USA) in 2001, working with a mouse mutant called *scurfy* that dies of fatal autoimmunity, discovered the FOXP3 gene — the "master switch" that tells a T cell to become a regulator rather than an attacker ([Brunkow 2001, Nat Genet](https://pubmed.ncbi.nlm.nih.gov/11138001/)). It was soon confirmed that humans with FOXP3 mutations develop IPEX syndrome — a severe multi-system autoimmune disease that appears in the first months of life.

Three years later, all three groups connected the dots: FOXP3 is precisely the master regulator that makes Sakaguchi's regulatory cells what they are ([Fontenot 2003, Nat Immunol](https://pubmed.ncbi.nlm.nih.gov/12612578/), [Hori 2003, Science](https://pubmed.ncbi.nlm.nih.gov/12522256/)).

Why this matters for multiple sclerosis

Multiple sclerosis is not an infection or a tumour — it is an autoimmune disease, in which the patient's own T cells and B cells wrongly recognise myelin (the protective sheath around nerve fibres) as a foreign invader and attack it ([Reich, Lucchinetti, Calabresi — NEJM 2018](https://pubmed.ncbi.nlm.nih.gov/29320652/)). MS research has shown for decades that people with MS have regulatory T cells that do not work as they should — they are present in normal numbers but are "weakened" and fail to silence the attacking cells ([Viglietta 2004, J Exp Med](https://pubmed.ncbi.nlm.nih.gov/15067033/), [Dominguez-Villar & Hafler 2018, Nat Immunol](https://pubmed.ncbi.nlm.nih.gov/29925996/)). This Nobel-winning discovery gives a molecular explanation of why that happens — and concrete drug targets.

What it means for future therapies — Treg therapy

The goal of the next generation of drugs is no longer just to "kill the bad immune cells" (which is what current DMTs like ocrelizumab or cladribine do), but to boost the natural brakes of the immune system. Three lines of development:

- Low-dose IL-2 — interleukin-2 in a low dose selectively feeds Treg cells. Trials in type 1 diabetes, lupus and MS already show 30–80% expansion of Tregs without activating attacking cells ([Rosenzwajg 2019, Ann Rheum Dis](https://pubmed.ncbi.nlm.nih.gov/30297332/), [TRANSREG trial](https://clinicaltrials.gov/study/NCT01988506)).

- Adoptive Treg transfer — a patient's blood sample is taken, their own Treg cells isolated, expanded in the lab to billions, and infused back. Early results in MS and organ transplantation are encouraging ([Chwojnicki 2021 in MS](https://pubmed.ncbi.nlm.nih.gov/34113087/)).

- CAR-Treg therapy — Tregs are genetically "armed" with a receptor that homes them directly to myelin, where they switch off inflammation only where needed (not systemically). In preclinical MS models (EAE) this halts and reverses damage ([Kim 2018 and related preclinical work](https://pubmed.ncbi.nlm.nih.gov/29483581/)).

What does this mean in practice? The first Treg-based MS drugs are unlikely to reach routine clinical use before 2030–2032. But it is a paradigm shift — from "suppress immunity" to "restore normal balance". The National MS Society and MS Trust commentaries after the Nobel announcement underline the same point: hope for patients who do not respond to, or cannot tolerate, today's DMTs, and for those with progressive MS where options remain limited ([National MS Society — comment](https://www.nationalmssociety.org/), [MS Trust](https://mstrust.org.uk/)).

What this does NOT mean

- Not a drug available tomorrow. Treg therapy trials in MS are currently in phase 1/2, which means 5–8 years to a potential approval.

- Do not stop your current therapy. Ocrelizumab, ofatumumab, natalizumab, cladribine and other DMTs remain the standard — see [MS DMTs in 2026](/en/blog/dmt-lekovi-multipla-skleroza-2026).

- MS is not "solved". This discovery explains one key mechanism of autoimmunity. Other pieces — Epstein-Barr virus ([article](/en/blog/epstein-barr-virus-multipla-skleroza)), low vitamin D ([article](/en/blog/vitamin-d-tezina-ms)), smoking, genetics — are still part of the puzzle.

The bigger picture — millions of people with autoimmune disease

The Karolinska Institute and Nobel committee estimate that the discoveries by Brunkow, Ramsdell and Sakaguchi have the potential to change treatment of more than 80 autoimmune diseases that affect about 4% of the world's population ([NobelPrize.org — popular science 2025](https://www.nobelprize.org/prizes/medicine/2025/popular-information/)). That includes:

- Multiple sclerosis (~2.9 million people worldwide, [MSIF Atlas](https://www.atlasofms.org/))

- Type 1 diabetes (~9 million)

- Rheumatoid arthritis (~18 million)

- Lupus, Crohn's disease, ulcerative colitis, psoriasis, autoimmune thyroiditis, coeliac disease, myasthenia gravis…

- Organ-transplant rejection — Tregs are already being trialled to reduce the need for life-long immunosuppression.

What MS patients can do today

- Do not change your therapy because of one news story. Talk to your neurologist about Treg-based trials if you are interested.

- Follow clinical trials. Active studies in Serbia: [MS clinical trials in Serbia](/en/blog/klinicke-studije-multipla-skleroza-srbija). Globally: [ClinicalTrials.gov search "treg multiple sclerosis"](https://clinicaltrials.gov/search?cond=Multiple%20Sclerosis&term=treg).

- Optimise what is already proven today: vitamin D ([article](/en/blog/vitamin-d-tezina-ms)), regular sleep ([article](/en/blog/san-ms-kvalitetan-odmor)), stopping smoking, stress control ([article](/en/blog/upravljanje-stresom-ms)) — all of which already influence Treg function.

- Join a patient registry. Larger databases mean a faster path from new therapies to patients. More in [MS centres in Europe and Serbia](/en/blog/ms-centri-evropa-srbija-poredjenje).

The 2025 Nobel Prize in Physiology or Medicine is a historic moment for autoimmune medicine, and for multiple sclerosis in particular. Brunkow, Ramsdell and Sakaguchi did not find a cure — they found a rule of the game: the immune system has a built-in self-control system, and in autoimmune disease that system fails. Now that we know how it works, we can repair it. For people with MS this is not a promise for tomorrow, but it is the strongest scientific hope of the last decade, on par with the discovery of the role of Epstein-Barr virus (Bjornevik 2022). MS treatment is moving into an era where we will not have to choose between "too much immunity" and "too much immunosuppression" — we will learn to tell the body to find its own balance.

Sources

NobelPrize.org — The Nobel Prize in Physiology or Medicine 2025: https://www.nobelprize.org/prizes/medicine/2025/. Press release: https://www.nobelprize.org/prizes/medicine/2025/press-release/. Popular information: https://www.nobelprize.org/prizes/medicine/2025/popular-information/. Sakaguchi S, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains. J Immunol. 1995: https://pubmed.ncbi.nlm.nih.gov/7636184/. Brunkow ME, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001: https://pubmed.ncbi.nlm.nih.gov/11138001/. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003: https://pubmed.ncbi.nlm.nih.gov/12612578/. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003: https://pubmed.ncbi.nlm.nih.gov/12522256/. Viglietta V, et al. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004: https://pubmed.ncbi.nlm.nih.gov/15067033/. Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nat Immunol. 2018: https://pubmed.ncbi.nlm.nih.gov/29925996/. Rosenzwajg M, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases (TRANSREG). Ann Rheum Dis. 2019: https://pubmed.ncbi.nlm.nih.gov/30297332/. Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. NEJM. 2018: https://pubmed.ncbi.nlm.nih.gov/29320652/. National MS Society: https://www.nationalmssociety.org/. MS Trust: https://mstrust.org.uk/. This article is informational and does not replace medical advice from your neurologist.