IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51353-2.html
   My bibliography  Save this article

Local administration of regulatory T cells promotes tissue healing

Author

Listed:
  • Bhavana Nayer

    (Monash University)

  • Jean L. Tan

    (Monash University)

  • Yasmin K. Alshoubaki

    (Monash University)

  • Yen-Zhen Lu

    (Monash University)

  • Julien M. D. Legrand

    (Monash University)

  • Sinnee Lau

    (Monash University)

  • Nan Hu

    (Monash University)

  • Anthony J. Park

    (Monash University)

  • Xiao-Nong Wang

    (Newcastle University)

  • Daniela Amann-Zalcenstein

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Peter F. Hickey

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Trevor Wilson

    (Monash Health Translation Precinct)

  • Gisela A. Kuhn

    (ETH Zurich)

  • Ralph Müller

    (ETH Zurich)

  • Ajithkumar Vasanthakumar

    (Olivia Newton-John Cancer Research Institute
    La Trobe University
    The University of Melbourne)

  • Shizuo Akira

    (Osaka University)

  • Mikaël M. Martino

    (Monash University
    Osaka University
    Monash University)

Abstract

Regulatory T cells (Tregs) are crucial immune cells for tissue repair and regeneration. However, their potential as a cell-based regenerative therapy is not yet fully understood. Here, we show that local delivery of exogenous Tregs into injured mouse bone, muscle, and skin greatly enhances tissue healing. Mechanistically, exogenous Tregs rapidly adopt an injury-specific phenotype in response to the damaged tissue microenvironment, upregulating genes involved in immunomodulation and tissue healing. We demonstrate that exogenous Tregs exert their regenerative effect by directly and indirectly modulating monocytes/macrophages (Mo/MΦ) in injured tissues, promoting their switch to an anti-inflammatory and pro-healing state via factors such as interleukin (IL)-10. Validating the key role of IL-10 in exogenous Treg-mediated repair and regeneration, the pro-healing capacity of these cells is lost when Il10 is knocked out. Additionally, exogenous Tregs reduce neutrophil and cytotoxic T cell accumulation and IFN-γ production in damaged tissues, further dampening the pro-inflammatory Mo/MΦ phenotype. Highlighting the potential of this approach, we demonstrate that allogeneic and human Tregs also promote tissue healing. Together, this study establishes exogenous Tregs as a possible universal cell-based therapy for regenerative medicine and provides key mechanistic insights that could be harnessed to develop immune cell-based therapies to enhance tissue healing.

Suggested Citation

  • Bhavana Nayer & Jean L. Tan & Yasmin K. Alshoubaki & Yen-Zhen Lu & Julien M. D. Legrand & Sinnee Lau & Nan Hu & Anthony J. Park & Xiao-Nong Wang & Daniela Amann-Zalcenstein & Peter F. Hickey & Trevor , 2024. "Local administration of regulatory T cells promotes tissue healing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51353-2
    DOI: 10.1038/s41467-024-51353-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51353-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51353-2?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. Dhanushika Ratnayake & Phong D. Nguyen & Fernando J. Rossello & Verena C. Wimmer & Jean L. Tan & Laura A. Galvis & Ziad Julier & Alasdair J. Wood & Thomas Boudier & Abdulsalam I. Isiaku & Silke Berger, 2021. "Macrophages provide a transient muscle stem cell niche via NAMPT secretion," Nature, Nature, vol. 591(7849), pages 281-287, March.
    2. Minako Ito & Kyoko Komai & Setsuko Mise-Omata & Mana Iizuka-Koga & Yoshiko Noguchi & Taisuke Kondo & Ryota Sakai & Kazuhiko Matsuo & Takashi Nakayama & Osamu Yoshie & Hiroko Nakatsukasa & Shunsuke Chi, 2019. "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery," Nature, Nature, vol. 565(7738), pages 246-250, January.
    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. Felicia Lazure & Rick Farouni & Korin Sahinyan & Darren M. Blackburn & Aldo Hernández-Corchado & Gabrielle Perron & Tianyuan Lu & Adrien Osakwe & Jiannis Ragoussis & Colin Crist & Theodore J. Perkins , 2023. "Transcriptional reprogramming of skeletal muscle stem cells by the niche environment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Nils Dennhag & Abraha Kahsay & Itzel Nissen & Hanna Nord & Maria Chermenina & Jiao Liu & Anders Arner & Jing-Xia Liu & Ludvig J. Backman & Silvia Remeseiro & Jonas Hofsten & Fatima Pedrosa Domellöf, 2024. "fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Rhonda L. McFleder & Anastasiia Makhotkina & Janos Groh & Ursula Keber & Fabian Imdahl & Josefina Peña Mosca & Alina Peteranderl & Jingjing Wu & Sawako Tabuchi & Jan Hoffmann & Ann-Kathrin Karl & Axel, 2023. "Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Jin Liu & Lihong Pan & Wenxuan Hong & Siqin Chen & Peiyuan Bai & Wei Luo & Xiaolei Sun & Furong He & Xinlin Jia & Jialiang Cai & Yingjie Chen & Kai Hu & Zhenju Song & Junbo Ge & Aijun Sun, 2022. "GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Stefano Suzzi & Tommaso Croese & Adi Ravid & Or Gold & Abbe R. Clark & Sedi Medina & Daniel Kitsberg & Miriam Adam & Katherine A. Vernon & Eva Kohnert & Inbar Shapira & Sergey Malitsky & Maxim Itkin &, 2023. "N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Mark Walkenhorst & Jana K. Sonner & Nina Meurs & Jan Broder Engler & Simone Bauer & Ingo Winschel & Marcel S. Woo & Lukas Raich & Iris Winkler & Vanessa Vieira & Lisa Unger & Gabriela Salinas & Olivie, 2024. "Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Nicolas Denans & Nhung T. T. Tran & Madeleine E. Swall & Daniel C. Diaz & Jillian Blanck & Tatjana Piotrowski, 2022. "An anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury in zebrafish," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Allah Nawaz & Muhammad Bilal & Shiho Fujisaka & Tomonobu Kado & Muhammad Rahil Aslam & Saeed Ahmed & Keisuke Okabe & Yoshiko Igarashi & Yoshiyuki Watanabe & Takahide Kuwano & Koichi Tsuneyama & Ayumi , 2022. "Depletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration," Nature Communications, Nature, vol. 13(1), pages 1-12, 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:15:y:2024:i:1:d:10.1038_s41467-024-51353-2. 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.