Drug Des Devel Ther. 2026 Aug 25;20:640423. doi: 10.2147/DDDT.S640423. eCollection 2026.
ABSTRACT
The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi in recognition of their pioneering contributions to the field of regulatory T cells (Tregs) and peripheral immune tolerance-defining Tregs as the core regulatory subset maintaining immune homeostasis and identifying the transcription factor FOXP3 as decisive for Treg development and functional maintenance, which lays the foundation for elucidating the mechanisms of immune imbalance-related diseases. As a novel bioactive molecule, molecular hydrogen (H2) possesses advantages of antioxidation, low toxicity, and multiple administration routes. Preliminary and accumulating studies suggest that H2 may protect Tregs' survival, enhance their proliferative activity and immunosuppressive function by inhibiting oxidative stress, regulating inflammatory signaling pathways (eg, NF-κB, TGF-β/Smad), and modulating apoptotic pathways. Integrating the core findings of the Nobel Prize, this review systematically summarizes the molecular mechanisms underlying H2-mediated Treg regulation, collates disease-specific evidence in autoimmune diseases, chronic inflammation, tissue injury repair, and other scenarios, analyzes the heterogeneous characteristics of Treg regulation mediated by different administration routes, and dissects current research limitations and clinical translation bottlenecks. It is important to emphasize that the available clinical support for H2-mediated Treg regulation is restricted to single case reports and small-scale exploratory open-label studies, which represent hypothesis-generating rather than hypothesis-confirming evidence. Finally, this review outlines the development direction of H2 combined with Treg-targeted strategies, noting that the current evidence remains preliminary and inconclusive, providing a new theoretical basis and technical insights for the precise treatment of immune-related diseases.
PMID:42668873 | PMC:PMC13525816 | DOI:10.2147/DDDT.S640423