@article{5891,
  keywords = {Autoimmune Diseases, Experimental models of disease, Pituitary diseases, Stem-cell biotechnology},
  author = {Keitaro Kanie and Takeshi Ito and Genzo Iguchi and Ryusaku Matsumoto and Keiko Muguruma and Shin Urai and Shuichi Kitayama and Hironori Bando and Masaaki Yamamoto and Hidenori Fukuoka and Wataru Ogawa and Shin Kaneko and Yutaka Takahashi},
  title = {Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid},
  abstract = {Anti-pituitary-specific transcription factor (PIT)−1 hypophysitis is an autoimmune disease characterized by hormone secretion impairment from PIT-1-expressing pituitary cells, accompanied by malignancies with ectopic PIT-1 expression. Cytotoxic T cells (CTL) targeting PIT-1-positive cells have been implicated in disease development, yet direct evidence is lacking. As human leukocyte antigen (HLA)-matching is required for modeling T cell-mediated autoimmune diseases, we employ induced pluripotent stem cells (iPSC) to generate pituitary organoids harboring the patients’ HLA haplotype and coculture the organoids with PIT-1-reactive CTLs isolated from the patients’ peripheral blood mononuclear cells. The coculture demonstrates specific CTL-mediated cytotoxicity against PIT-1-positive cells exclusively in autologous conditions, with this cytotoxicity inhibited by immunosuppressive agents such as dexamethasone and cyclosporin A. Multiple combinations of epitopes, CTLs, and HLA molecules are responsible for pathogenesis. These data demonstrate CTL-mediated autoimmunity in anti-PIT-1 hypophysitis and highlight the potential application of this strategy for other T cell-mediated autoimmune diseases.},
  year = {2025},
  journal = {Nature Communications},
  volume = {16},
  pages = {7900},
  month = {2025-08-25},
  issn = {2041-1723},
  url = {https://www.nature.com/articles/s41467-025-63183-x},
  doi = {10.1038/s41467-025-63183-x},
  language = {en},
}