TY - JOUR
KW - Autoimmune Diseases
KW - Experimental models of disease
KW - Pituitary diseases
KW - Stem-cell biotechnology
AU - Keitaro Kanie
AU - Takeshi Ito
AU - Genzo Iguchi
AU - Ryusaku Matsumoto
AU - Keiko Muguruma
AU - Shin Urai
AU - Shuichi Kitayama
AU - Hironori Bando
AU - Masaaki Yamamoto
AU - Hidenori Fukuoka
AU - Wataru Ogawa
AU - Shin Kaneko
AU - Yutaka Takahashi
AB - 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.
BT - Nature Communications
DA - 2025-08-25
DO - 10.1038/s41467-025-63183-x
IS - 1
LA - en
N2 - 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.
PY - 2025
EP - 7900
T2 - Nature Communications
TI - Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid
UR - https://www.nature.com/articles/s41467-025-63183-x
VL - 16
Y2 - 2025-08-25
SN - 2041-1723
ER -