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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.
Bluestone et al. (Thu,) studied this question.