Regulatory T cells: master orchestrators of immune tolerance and tissue homeostasis
9 affiliations
- 1Diabetes Center, University of California, San Francisco
- 2BC Children’s Hospital Research Institute
- 3Department of Surgery, Faculty of Medicine, University of British Columbia
- 4School of Biomedical Engineering, Faculty of Applied Science, University of British Columbia
- 5Sonoma Biotherapeutics
- 6Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- 7Diabetes Center, Department of Surgery, and Gladstone-UCSF Institute of Genome Immunology, University of California, San Francisco
- 8Department of Medical Immunology, Medical University of Gdańsk
- 9PolTREG S.A
Abstract
Harnessing the biology of regulatory T cells (Tregs) for therapeutic development is one of medicine’s most promising opportunities to transform disease treatment. Initially viewed simply as guardians against destructive immune responses, we now understand that Tregs are adaptive and highly specialized coordinators of immune tolerance and tissue repair. This strategic roadmap examines how evolving insights into their central role in maintaining tolerance and health can transform therapeutic development across medical specialties. Early efforts to evaluate Treg therapies have proven safe and shown some clinical benefit. The convergence of biological insights and technological advances has the potential to harness and exploit this specialized tolerogenic population by augmenting function through environmental cues and reinforcing tissue-repair capabilities. Advanced engineering approaches can now endow Treg therapies with antigen-specificity, enforce suppressive programming, and enable off-the-shelf or in vivo gene therapy opportunities. This new class of therapeutics promises to shift treatment paradigms from lifelong management to drug-free durable remissions or even cures for diseases currently requiring chronic immunosuppression. The recognition that dysregulated inflammation underlies countless human diseases opens unprecedented possibilities for treating intractable conditions across specialties—from transplantation and autoimmunity, metabolic disorders and cardiovascular disease, to neurodegeneration and even aging itself. Realizing the potential of Treg-based therapies remains a primary goal for the field, representing a strategic shift from systemic immunosuppression to precision tolerance restoration as a unifying therapeutic paradigm.
Related
- IL-2-Producing Tfh Cells Sustain Treg Cell Homeostasis and Immune Tolerance in the Gut
- Regulatory T cell therapy and immune tolerance in heart transplantation: a translational evidence framework for regulatory T cells-cell characterization and recipient-graft monitoring
- CD19 CAR Engineered T Regulatory Cells Promote Durable Immune Tolerance in Experimental Systemic Lupus Erythematosus
- Cancer-associated fibroblasts and innate immune cells: orchestrators of the immunosuppressive tumor microenvironment
- Ion regulatory mechanisms supporting hypersaline tolerance in the coastal rock pool mosquito Aedes togoi
BibTeX
@article{bluestone2026regulatory,
title = {{Regulatory T cells: master orchestrators of immune tolerance and tissue homeostasis}},
author = {Jeffrey A. Bluestone and Megan K. Levings and F J Ramsdell and Alexander Yu Rudensky and Qizhi Tang and Piotr Trzonkowski},
journal = {Frontiers in Science},
year = {2026},
month = jun,
doi = {10.3389/fsci.2026.1792210},
url = {https://doi.org/10.3389/fsci.2026.1792210},
note = {CC BY},
}
RIS
TY - JOUR
TI - Regulatory T cells: master orchestrators of immune tolerance and tissue homeostasis
AU - Jeffrey A. Bluestone
AU - Megan K. Levings
AU - F J Ramsdell
AU - Alexander Yu Rudensky
AU - Qizhi Tang
AU - Piotr Trzonkowski
PY - 2026
DA - 2026/06/25
JO - Frontiers in Science
DO - 10.3389/fsci.2026.1792210
UR - https://doi.org/10.3389/fsci.2026.1792210
AB - Harnessing the biology of regulatory T cells (Tregs) for therapeutic development is one of medicine’s most promising opportunities to transform disease treatment. Initially viewed simply as guardians against destructive immune responses, we now understand that Tregs are adaptive and highly specialized coordinators of immune tolerance and tissue repair. This strategic roadmap examines how evolving insights into their central role in maintaining tolerance and health can transform therapeutic development across medical specialties. Early efforts to evaluate Treg therapies have proven safe and shown some clinical benefit. The convergence of biological insights and technological advances has the potential to harness and exploit this specialized tolerogenic population by augmenting function through environmental cues and reinforcing tissue-repair capabilities. Advanced engineering approaches can now endow Treg therapies with antigen-specificity, enforce suppressive programming, and enable off-the-shelf or in vivo gene therapy opportunities. This new class of therapeutics promises to shift treatment paradigms from lifelong management to drug-free durable remissions or even cures for diseases currently requiring chronic immunosuppression. The recognition that dysregulated inflammation underlies countless human diseases opens unprecedented possibilities for treating intractable conditions across specialties—from transplantation and autoimmunity, metabolic disorders and cardiovascular disease, to neurodegeneration and even aging itself. Realizing the potential of Treg-based therapies remains a primary goal for the field, representing a strategic shift from systemic immunosuppression to precision tolerance restoration as a unifying therapeutic paradigm.
SN - 2813-6330
ER -