“Peacemaker” immune cells could help treat diseases ranging from type 1 diabetes to neurodegeneration by restoring immune tolerance, a paper published in December 2016 said. frontiers of science.
Inflammation is increasingly being cited as a cause of a wide range of diseases, from cancer, diabetes and chronic infections to cardiovascular, neurodegenerative and reproductive diseases. Immune cells called regulatory T cells (Tregs) were originally defined as “suppressor” cells that prevent other immune cells from attacking the body, but are eventually being studied as “living drugs” that can be adapted to target many diseases that have an inflammatory component.
Such approaches aimed at tailoring Treg therapy to specific diseases and tissues may support more precise control of immune responses. In autoimmune diseases and transplant rejection, Tregs may even help shift treatment from widespread immunosuppression, which poses myriad risks, to restoration of immune tolerance and long-term disease control.
Uncontrolled inflammation is at the root of so many human diseases, and Tregs that can address it offer one of the most exciting opportunities in modern medicine. Tregs also help regulate immunity, going far beyond their traditional suppressor roles, such as tissue repair, stabilizing metabolism, and suppressing inflammation. That makes them incredibly powerful as living medicines. ”
Dr. Jeffrey Bluestone, co-lead author, co-founder, and scientific advisor, Sonoma Biotherapeutics
“New genetic engineering and smart combinatorial approaches are transforming the way immune tolerance is restored and maintained. This is just the beginning,” said co-author Dr. Fred Ramsdell, winner of the 2025 Nobel Prize in Physiology or Medicine for his discoveries in immune tolerance and co-founder and advisor of Sonoma Biotherapeutics.
Personalized and precise treatment
Researchers are studying Tregs in a wide range of conditions associated with dysregulation of immune tolerance, including autoimmune diseases and chronic inflammation, as well as cancer, severe COVID-19, neurodegeneration, metabolic diseases, fibrosis, aging, pregnancy-related diseases, and autoimmunity.
However, the role of Tregs varies depending on the disease. Cancers can suppress harmful inflammation to prevent autoimmunity and degenerative conditions, and cancers can exploit these same immune tolerance mechanisms to evade immune attack. This paper describes how the next generation of recombinant Treg therapies will ultimately be designed to either restore or selectively destroy resistance, depending on the disease context.
Current standard treatments for autoimmune diseases and transplant rejection typically focus on suppressing the immune system with powerful drugs, often targeting dangerous immune responses long after tissue damage has occurred. Therefore, restoring immune tolerance rather than simply managing symptoms is highly appealing.
Initial evaluation of Tregs in autoimmunity and transplant rejection has shown good tolerance and safety profiles, as well as being associated with early signs of clinical benefit.
According to the researchers, the next frontier is to achieve true precision by tailoring treatments with three tiers of specificity:
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Accurate patient selection: Match patients to treatments based on immune subtype, disease stage, or predictive biomarkers.
Dr. Ramsdell said, “Ultimately, success will depend on precision: delivering the right Tregs, in the right way, to the right tissue, at the right time. This is the foundation that will allow tolerance-based medicine to be extended to a very wide range of human diseases.”
Opening the door to patient care for patients
Maximizing impact for many patients will depend on successfully enhancing Treg function, enhancing the response of these cells to environmental cues and reinforcing the cells’ natural role in tissue repair. Advances are accelerating thanks to new engineering tools, allowing scientists to develop off-the-shelf Treg therapies and explore gene-based approaches that can program these cells in the body. Together, these innovations are laying the foundation for a new generation of precision resistance-reversing drugs, the authors say.
The authors emphasize that advancing tolerance medicine requires advancing several approaches simultaneously. Combination strategies combine Tregs with cytokines or immunomodulators to provide the most immediate method to increase Tregs persistence, enhance function, and reduce inflammatory pressure. As engineering, metabolic regulation, and tissue targeting technologies mature, these elements could be added to existing therapeutic platforms to improve stability, enhance homing, and enhance tissue repair, the paper says.
Co-author Qizhi Tang, a professor at the University of California, San Francisco, said: “The technical foundations are being laid, and we may soon be able to shift treatment from broad immunosuppression to true and precise restoration of tolerance.”
Finally, the authors highlight how strategic investments are critical to moving tolerance medicine from a concept to a reality with cross-sector collaborations, regulatory partnerships, and sustained funding at scale for both development and clinical access.
“With continued investment, cell-based therapies like Tregs could become a new pillar of medicine alongside small molecules, biologics, and gene therapies, unlocking treatments for diseases once thought incurable,” said co-author Professor Megan Levings of the University of British Columbia and Children’s Hospital Research Institute of British Columbia.
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Reference magazines:
Bluestone, J.A. others. (2026). Regulatory T cells: masters of regulating immune tolerance and tissue homeostasis. frontiers of science. DOI: 10.3389/fsci.2026.1792210. https://www.frontiersin.org/journals/science/articles/10.3389/fsci.2026.1792210/full
