biostudies-literatureKanie KMEXT | Japan Society for the Promotion of ScienceMEXT | Japan Society for the Promotion of Science (JSPS)Japan Agency for Medical Research and DevelopmentJapan Agency for Medical Research and Development (AMED)7900https://www.ebi.ac.uk/biostudies/studies/S-EPMC12378982biostudies-literatureUnknown16(1)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 excNature communicationsModeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.PMC1237898218K08514, 23659477, 21K20933, and 22K1639617bm0804012h0001Ito TMatsumoto RYamamoto MMuguruma KKitayama SKanie KKaneko STakahashi YIguchi GOgawa WUrai SFukuoka HBando HfalseModeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.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 exc2025-01-01T00:00:00Z2025 Aug2026-07-15T12:47:15.34Z2026-07-04T03:15:56.913ZS-EPMC123789824085507110.1038/s41467-025-63183-x