A research group at the Keio University School of Medicine has developed a novel antigen-specific immunotherapy for the autoimmune disease pemphigus vulgaris (PV). The group was led by Professor Masayuki Amagai (Director, RIKEN IMS), Associate Professor Hayato Takahashi, and Research Fellow Miho Mukai of the Department of Dermatology, Keio University School of Medicine, in collaboration with Professor Shimon Sakaguchi and Associate Professor Norihisa Mikami (Regcell Co., Ltd.) of the University of Osaka.
Using an induction method originally developed at the University of Osaka, the team successfully converted disease-causing T cells into stable and functional induced regulatory T cells (S/F-iTregs) that specifically recognize desmoglein 3 (Dsg3)—the autoantigen responsible for PV. In a mouse model, treatment with these Dsg3-specific S/F-iTregs markedly reduced disease severity and autoantibody levels, demonstrating precise, antigen-specific immune suppression. Importantly, the researchers also generated similar S/F-iTregs from the peripheral blood T cells of patients with pemphigus vulgaris not by genetic engineering, but through pharmacological and epigenetic reprogramming that stabilizes Foxp3 expression and confers durable regulatory function. These patient-derived S/F-iTregs effectively suppressed T-cell proliferation in vitro, demonstrating their therapeutic potential.
This study establishes a foundation for next-generation, antigen-specific, and non-genetic cell therapy for autoimmune diseases, providing a new approach to reprogram disease-causing T cells into stable, antigen-specific regulatory cells with high safety and precision.
These findings were published online in the international journal Science Translational Medicine on October 22, 2025 (Eastern Standard Time).
