IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10106-2.html
   My bibliography  Save this article

Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus

Author

Listed:
  • Christopher A. Odhams

    (King’s College London
    Queen Mary University of London)

  • Amy L. Roberts

    (King’s College London
    King’s College London)

  • Susan K. Vester

    (King’s College London)

  • Carolina S. T. Duarte

    (King’s College London)

  • Charlie T. Beales

    (King’s College London)

  • Alexander J. Clarke

    (University of Oxford)

  • Sonja Lindinger

    (King’s College London
    University of Applied Sciences - FH Campus Wien
    Johannes Kepler University Linz)

  • Samuel J. Daffern

    (King’s College London
    University of Cambridge)

  • Antonino Zito

    (King’s College London)

  • Lingyan Chen

    (King’s College London
    University of Cambridge)

  • Leonardo L. Jones

    (King’s College London)

  • Lora Boteva

    (King’s College London
    University of Edinburgh Western General Hospital)

  • David L. Morris

    (King’s College London)

  • Kerrin S. Small

    (King’s College London)

  • Michelle M. A. Fernando

    (King’s College London)

  • Deborah S. Cunninghame Graham

    (King’s College London)

  • Timothy J. Vyse

    (King’s College London)

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterised by increased expression of type I interferon (IFN)-regulated genes and a striking sex imbalance towards females. Through combined genetic, in silico, in vitro, and ex vivo approaches, we define CXorf21, a gene of hitherto unknown function, which escapes X-chromosome inactivation, as a candidate underlying the Xp21.2 SLE association. We demonstrate that CXorf21 is an IFN-response gene and that the sexual dimorphism in expression is magnified by immunological challenge. Fine-mapping reveals a single haplotype as a potential causal cis-eQTL for CXorf21. We propose that expression is amplified through modification of promoter and 3′-UTR chromatin interactions. Finally, we show that the CXORF21 protein colocalises with TLR7, a pathway implicated in SLE pathogenesis. Our study reveals modulation in gene expression affected by the combination of two hallmarks of SLE: CXorf21 expression increases in a both an IFN-inducible and sex-specific manner.

Suggested Citation

  • Christopher A. Odhams & Amy L. Roberts & Susan K. Vester & Carolina S. T. Duarte & Charlie T. Beales & Alexander J. Clarke & Sonja Lindinger & Samuel J. Daffern & Antonino Zito & Lingyan Chen & Leonar, 2019. "Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10106-2
    DOI: 10.1038/s41467-019-10106-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10106-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-019-10106-2?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
    ---><---

    Citations

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


    Cited by:

    1. Andras Boeszoermenyi & Léa Bernaleau & Xudong Chen & Felix Kartnig & Min Xie & Haobo Zhang & Sensen Zhang & Maeva Delacrétaz & Anna Koren & Ann-Katrin Hopp & Vojtech Dvorak & Stefan Kubicek & Daniel A, 2023. "A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Xudong Chen & Min Xie & Sensen Zhang & Marta Monguió-Tortajada & Jian Yin & Chang Liu & Youqi Zhang & Maeva Delacrétaz & Mingyue Song & Yixue Wang & Lin Dong & Qiang Ding & Boda Zhou & Xiaolin Tian & , 2023. "Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Chao Yang & Mahesh Bachu & Yong Du & Caroline Brauner & Ruoxi Yuan & Marie Dominique Ah Kioon & Giancarlo Chesi & Franck J. Barrat & Lionel B. Ivashkiv, 2022. "CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes," Nature Communications, Nature, vol. 13(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_s41467-019-10106-2. 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.

    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.