Peacemaker immune cells offer new hope for restoring immune tolerance

'Peacemaker' immune cells could help treat diseases ranging from type 1 diabetes to neurodegeneration by restoring immune tolerance, according to a new paper in Frontiers in Science. 

From cancer, diabetes, and chronic infections, to cardiovascular, neurodegenerative, and reproductive conditions, inflammation is increasingly cited as a driver of a broad range of diseases. Immune cells called regulatory T cells (Tregs)-originally defined as "suppressor" cells that stop other immune cells from attacking the body-are being explored as "living drugs" that could eventually be adapted to target many diseases with an inflammatory component. 

Such an approach, which aims to tailor Treg therapies to specific diseases and tissues, could support more precise control of immune responses. In autoimmune diseases and transplant rejection, Tregs could even help shift treatment from broad immunosuppression, which brings myriad risks, toward restored immune tolerance and longer-term disease control. 

Uncontrolled inflammation sits at the root of so many human diseases, so Tregs that can tackle this offer some of the most exciting opportunities in modern medicine. Tregs can also help control immunity far beyond their classical suppressor role-helping repair tissue, stabilize metabolism, and keep inflammation in check. That makes them incredibly powerful as living medicines." 

Dr. Jeffrey Bluestone, joint lead author, co-founder and scientific advisor to Sonoma Biotherapeutics

Joint lead author Dr Fred Ramsdell, who won the 2025 Nobel Prize for Physiology or Medicine for his discoveries around immune tolerance, and is also a co-founder and advisor to Sonoma Biotherapeutics, said: "With emerging genetic engineering and smart combination approaches, we're on the cusp of transforming how immune tolerance is restored and maintained. This really is only the beginning." 

Personalized, precision treatments 

Researchers are investigating Tregs in a broad range of conditions linked to dysregulated immune tolerance in autoimmune diseases and chronic inflammation, as well as cancer, severe COVID-19, neurodegeneration, metabolic disease, fibrosis, aging, pregnancy-related disorders, and autoimmunity. 

However, the role of Tregs differs across diseases. While they can suppress damaging inflammation to prevent autoimmune and degenerative conditions, cancers can exploit these same immune tolerance mechanisms to evade immune attack. The paper describes how next-generation engineered Treg therapies could eventually be designed either to restore tolerance or selectively disrupt it, depending on the disease context. 

Current standard of care for autoimmune conditions and transplant rejection typically focuses on suppressing the immune system with powerful drugs-often targeting dangerous immune responses long after tissue damage has occurred. Restoring immune tolerance, rather than simply managing symptoms, is therefore highly appealing. 

Early evaluations of Tregs in autoimmunity and transplant rejection have shown good tolerance and safety profiles, as well as being linked to early signs of clinical benefit. 

The next frontier, the researchers say, is achieving true precision by tailoring treatments with three layers of specificity: 

• Precision in the therapy itself: designing agents that affect the right target and stay stable and effective over time 

• Precision in tissue activity and timing 

• Precision in patient selection: matching patients to therapies based on immune subtype, disease stage, or predictive biomarkers. 

Dr Ramsdell said: "Ultimately, success will come down to precision: the right Treg, delivered in the right way, to the right tissue, at the right time. That's the foundation that could extend tolerance-based medicine across an extraordinary range of human diseases." 

Unlocking tolerance medicine for patients 

Maximizing impact for many patients depends on successfully enhancing Treg function-strengthening the response of these cells to environmental cues and reinforcing their natural role in tissue repair. New engineering tools are speeding up progress, allowing scientists to develop off-the-shelf Treg therapies and explore gene-based approaches that could program these cells inside the body. Together, say the authors, these innovations are laying the foundation for a new generation of precision tolerance-restoring medicines. 

Moving tolerance medicine forward will require several approaches to advance at the same time, stress the authors. Combination strategies offer the most immediate path, pairing Tregs with cytokines or immunomodulatory agents that boost their persistence, strengthen function, or reduce inflammatory pressure. As engineering, metabolic tuning, and tissue targeting technologies mature, these elements could be added to existing therapeutic platforms to improve stability, enhance homing, and reinforce tissue repair, according to the paper. 

Co-author Prof Qizhi Tang, from University of California San Francisco, said: "The technical foundations have been laid, and we may soon be able to transform treatment from broad immunosuppression to restoring true precision tolerance." 

Finally, the authors highlight how strategic investment will be crucial to move tolerance medicine from concept to reality-powering cross-disciplinary collaboration, regulatory partnership, and sustained funding as both development and clinical access scales. 

Co-author Prof Megan Levings from University of British Columbia and BC Children's Hospital Research Institute said: "With continued investment, cell-based therapies like Tregs could become a new pillar of medicine-standing alongside small molecules, biologics and gene therapies, and unlocking treatments for diseases once thought incurable."