iPSCs engrafted in allogeneic hosts without immunosuppression induce donor- specific tolerance to secondary allografts
成果类型：
Article
署名作者：
Kamatani, Tomoki; Kimura, Reiko; Ikeda, Satoshi; Inoue, Makoto; Seino, Ken-ichiro
署名单位：
Hokkaido University
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-14084
DOI：
10.1073/pnas.2413398122
发表日期：
2025-03-18
关键词：
embryonic stem-cells
differentiated derivatives
lymphoid neogenesis
progenitor cells
nervous-system
t-lymphocytes
transplantation
immunogenicity
acceptance
responses
摘要：
Currently, most cell or tissue transplantations using induced pluripotent stem cells (iPSCs) are anticipated to involve allogeneic iPSCs. However, the immunological properties of iPSCs in an allogeneic setting are not well understood. previously established a mouse transplantation model of MHC-compatible/minor antigen-mismatched combinations, assuming a hypoimmunogenic iPSC-setting. Here, we found that iPSCs subcutaneously inoculated into MHC-compatible geneic host mice resisted rejection and formed teratomas without immunosuppressant administration. Notably, when skin grafts were transplanted onto hosts more 40 d after the initial iPSCs inoculation, only the skin of the same strain as the initial iPSCs was engrafted. Therefore, donor-specific immune tolerance was induced a single iPSC inoculation. Diverse analyses, including single-cell RNA-sequencing after transplantation, revealed an increase in regulatory T cell (Treg) population, particularly CD25+CD103+ effector Tregs within the teratoma and skin grafts. The removal of CD25+ or Foxp3+ cells suppressed the increase in effector Tregs disrupted graft acceptance, indicating the importance of these cells in the establishment of immune tolerance. Within the teratoma, we observed an increase TGF-f32 levels, suggesting an association with the increase in effector Tregs. results provide important insights for future applications of allogeneic iPSC-based cell or tissue transplantation.