IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63183-x.html
   My bibliography  Save this article

Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid

Author

Listed:
  • Keitaro Kanie

    (Kobe University Graduate School of Medicine)

  • Takeshi Ito

    (Center for iPS Cell Research and Application (CiRA), Kyoto University)

  • Genzo Iguchi

    (Kobe University)

  • Ryusaku Matsumoto

    (CiRA, Kyoto University)

  • Keiko Muguruma

    (Kansai Medical University
    RIKEN Center for Biosystems Dynamics Research)

  • Shin Urai

    (Kobe University Graduate School of Medicine)

  • Shuichi Kitayama

    (Center for iPS Cell Research and Application (CiRA), Kyoto University)

  • Hironori Bando

    (Kobe University Hospital)

  • Masaaki Yamamoto

    (Kobe University Hospital)

  • Hidenori Fukuoka

    (Kobe University Hospital)

  • Wataru Ogawa

    (Kobe University Graduate School of Medicine)

  • Shin Kaneko

    (Center for iPS Cell Research and Application (CiRA), Kyoto University)

  • Yutaka Takahashi

    (Kobe University Hospital
    Nara Medical University)

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.

Suggested Citation

  • Keitaro Kanie & Takeshi Ito & Genzo Iguchi & Ryusaku Matsumoto & Keiko Muguruma & Shin Urai & Shuichi Kitayama & Hironori Bando & Masaaki Yamamoto & Hidenori Fukuoka & Wataru Ogawa & Shin Kaneko & Yut, 2025. "Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63183-x
    DOI: 10.1038/s41467-025-63183-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63183-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-63183-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chikafumi Ozone & Hidetaka Suga & Mototsugu Eiraku & Taisuke Kadoshima & Shigenobu Yonemura & Nozomu Takata & Yutaka Oiso & Takashi Tsuji & Yoshiki Sasai, 2016. "Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    2. Daniela Latorre & Ulf Kallweit & Eric Armentani & Mathilde Foglierini & Federico Mele & Antonino Cassotta & Sandra Jovic & David Jarrossay & Johannes Mathis & Francesco Zellini & Burkhard Becher & Ant, 2018. "T cells in patients with narcolepsy target self-antigens of hypocretin neurons," Nature, Nature, vol. 562(7725), pages 63-68, October.
    3. Sergey Nejentsev & Joanna M. M. Howson & Neil M. Walker & Jeffrey Szeszko & Sarah F. Field & Helen E. Stevens & Pamela Reynolds & Matthew Hardy & Erna King & Jennifer Masters & John Hulme & Lisa M. Ma, 2007. "Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A," Nature, Nature, vol. 450(7171), pages 887-892, December.
    4. Hidetaka Suga & Taisuke Kadoshima & Maki Minaguchi & Masatoshi Ohgushi & Mika Soen & Tokushige Nakano & Nozomu Takata & Takafumi Wataya & Keiko Muguruma & Hiroyuki Miyoshi & Shigenobu Yonemura & Yutak, 2011. "Self-formation of functional adenohypophysis in three-dimensional culture," Nature, Nature, vol. 480(7375), pages 57-62, December.
    5. Natasja Wulff Pedersen & Anja Holm & Nikolaj Pagh Kristensen & Anne-Mette Bjerregaard & Amalie Kai Bentzen & Andrea Marion Marquard & Tripti Tamhane & Kristoffer Sølvsten Burgdorf & Henrik Ullum & Pou, 2019. "CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hanna M. Ollila & Eilon Sharon & Ling Lin & Nasa Sinnott-Armstrong & Aditya Ambati & Selina M. Yogeshwar & Ryan P. Hillary & Otto Jolanki & Juliette Faraco & Mali Einen & Guo Luo & Jing Zhang & Fang H, 2023. "Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Vikash Chandra & Hazem Ibrahim & Clémentine Halliez & Rashmi B. Prasad & Federica Vecchio & Om Prakash Dwivedi & Jouni Kvist & Diego Balboa & Jonna Saarimäki-Vire & Hossam Montaser & Tom Barsby & Väin, 2022. "The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Hao Hu & Anthony N. Vomund & Orion J. Peterson & Neetu Srivastava & Tiandao Li & Lisa Kain & Wandy L. Beatty & Bo Zhang & Chyi-Song Hsieh & Luc Teyton & Cheryl F. Lichti & Emil R. Unanue & Xiaoxiao Wa, 2024. "Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Gregory J. Golden & Vincent H. Wu & Jacob T. Hamilton & Kevin R. Amses & Melanie R. Shapiro & Alberto Sada Japp & Chengyang Liu & M. Betina Pampena & Leticia Kuri-Cervantes & James J. Knox & Jay S. Ga, 2025. "Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    5. Alexia Carré & Fatoumata Samassa & Zhicheng Zhou & Javier Perez-Hernandez & Christiana Lekka & Anthony Manganaro & Masaya Oshima & Hanqing Liao & Robert Parker & Annalisa Nicastri & Barbara Brandao & , 2025. "Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    6. Hideki Ogura & Jin Gohda & Xiuyuan Lu & Mizuki Yamamoto & Yoshio Takesue & Aoi Son & Sadayuki Doi & Kazuyuki Matsushita & Fumitaka Isobe & Yoshihiro Fukuda & Tai-Ping Huang & Takamasa Ueno & Naomi Mam, 2022. "Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. repec:plo:pone00:0114486 is not listed on IDEAS
    8. Sylvain Perriot & Samuel Jones & Raphaël Genolet & Amandine Mathias & Helen Lindsay & Sara Bobisse & Giovanni Liberto & Mathieu Canales & Lise Queiroz & Christophe Sauvage & Ingrid Wagner & Larise Obe, 2025. "Neuron-reactive KIR+CD8+ T cells display an encephalitogenic transcriptional program in autoimmune encephalitis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63183-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.