IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13587-3.html
   My bibliography  Save this article

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

Author

Listed:
  • Martin G. Scherm

    (Helmholtz Diabetes Center at Helmholtz Zentrum München
    Deutsches Zentrum für Diabetesforschung (DZD))

  • Isabelle Serr

    (Helmholtz Diabetes Center at Helmholtz Zentrum München
    Deutsches Zentrum für Diabetesforschung (DZD))

  • Adam M. Zahm

    (University of Pennsylvania)

  • Jonathan Schug

    (University of Pennsylvania)

  • Saverio Bellusci

    (Universities of Giessen and Marburg Lung Center)

  • Rossella Manfredini

    (University of Modena and Reggio Emilia)

  • Victoria K. Salb

    (Helmholtz Diabetes Center at Helmholtz Zentrum München
    Deutsches Zentrum für Diabetesforschung (DZD))

  • Katharina Gerlach

    (University of Erlangen-Nuremberg)

  • Benno Weigmann

    (University of Erlangen-Nuremberg)

  • Anette-Gabriele Ziegler

    (Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health
    Technical University Munich, at Klinikum rechts der Isar)

  • Klaus H. Kaestner

    (University of Pennsylvania)

  • Carolin Daniel

    (Helmholtz Diabetes Center at Helmholtz Zentrum München
    Deutsches Zentrum für Diabetesforschung (DZD)
    Ludwig-Maximilians-Universität München)

Abstract

In type 1 diabetes, the appearance of islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in the destruction of pancreatic beta cells, molecular underpinnings promoting aberrant T cell activation remain poorly understood. Here, we show that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity and that its inhibition enhances Treg induction and stability, leading to reduced islet autoimmunity in non-obese diabetic mice. Using various cellular and molecular approaches we identify Tet2 as a direct target of miR142-3p, thereby linking high miR142-3p levels to epigenetic remodeling in Tregs. These findings offer a mechanistic model where during islet autoimmunity miR142-3p/Tet2-mediated Treg instability contributes to autoimmune activation and progression.

Suggested Citation

  • Martin G. Scherm & Isabelle Serr & Adam M. Zahm & Jonathan Schug & Saverio Bellusci & Rossella Manfredini & Victoria K. Salb & Katharina Gerlach & Benno Weigmann & Anette-Gabriele Ziegler & Klaus H. K, 2019. "miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13587-3
    DOI: 10.1038/s41467-019-13587-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13587-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13587-3?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ting Zhong & Xinyu Li & Kang Lei & Rong Tang & Qiaolin Deng & Paul E Love & Zhiguang Zhou & Bin Zhao & Xia Li, 2024. "TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:10:y:2019:i:1:d:10.1038_s41467-019-13587-3. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.