| RRC ID |
85796
|
| 著者 |
Kanie K, Ito T, Iguchi G, Matsumoto R, Muguruma K, Urai S, Kitayama S, Bando H, Yamamoto M, Fukuoka H, Ogawa W, Kaneko S, Takahashi Y.
|
| タイトル |
Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
16(1)
|
| ページ |
7900
|
| 公開日 |
2025-8-25
|
| DOI |
10.1038/s41467-025-63183-x
|
| PII |
10.1038/s41467-025-63183-x
|
| PMID |
40855071
|
| PMC |
PMC12378982
|
| MeSH |
Autoimmune Diseases* / immunology
Autoimmune Hypophysitis* / immunology
Autoimmune Hypophysitis* / pathology
Coculture Techniques
HLA Antigens / genetics
HLA Antigens / immunology
Humans
Immunosuppressive Agents / pharmacology
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / immunology
Induced Pluripotent Stem Cells* / metabolism
Octamer Transcription Factor-3
Organoids* / cytology
Organoids* / immunology
Pituitary Gland / immunology
Pituitary Gland / pathology
T-Lymphocytes, Cytotoxic* / immunology
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063)
409B2(HPS0076) |
| 遺伝子材料 |
Human HLA-A*02:01:01 cDNA (RDB02866)
Human HLA-A*11:01:01 cDNA (RDB02869) |
