IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-02862-4.html
   My bibliography  Save this article

IL-6 receptor blockade corrects defects of XIAP-deficient regulatory T cells

Author

Listed:
  • Wan-Chen Hsieh

    (Institute of Molecular Biology, Academia Sinica, Academia Sinica)

  • Tzu-Sheng Hsu

    (Institute of Molecular Biology, Academia Sinica, Academia Sinica)

  • Ya-Jen Chang

    (Institute of Biomedical Sciences, Academia Sinica)

  • Ming-Zong Lai

    (Institute of Molecular Biology, Academia Sinica, Academia Sinica)

Abstract

X-linked lymphoproliferative syndrome type-2 (XLP-2) is a primary immunodeficiency disease attributed to XIAP mutation and is triggered by infection. Here, we show that mouse Xiap−/− regulatory T (Treg) cells and human XIAP-deficient Treg cells are defective in suppressive function. The Xiap−/− Treg cell defect is linked partly to decreased SOCS1 expression. XIAP binds SOCS1 and promotes SOCS1 stabilization. Foxp3 stability is reduced in Xiap−/− Treg cells. In addition, Xiap−/− Treg cells are prone to IFN-γ secretion. Transfer of wild-type Treg cells partly rescues infection-induced inflammation in Xiap−/− mice. Notably, inflammation-induced reprogramming of Xiap−/− Treg cells can be prevented by blockade of the IL-6 receptor (IL-6R), and a combination of anti-IL-6R and Xiap−/− Treg cells confers survival to inflammatory infection in Xiap−/− mice. Our results suggest that XLP-2 can be corrected by combination treatment with autologous iTreg (induced Treg) cells and anti-IL-6R antibody, bypassing the necessity to transduce Treg cells with XIAP.

Suggested Citation

  • Wan-Chen Hsieh & Tzu-Sheng Hsu & Ya-Jen Chang & Ming-Zong Lai, 2018. "IL-6 receptor blockade corrects defects of XIAP-deficient regulatory T cells," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02862-4
    DOI: 10.1038/s41467-018-02862-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-02862-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-02862-4?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
    ---><---

    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:9:y:2018:i:1:d:10.1038_s41467-018-02862-4. 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.