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

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, Leonardo L. Jones, Lora Boteva, David L. Morris, Kerrin S. Small, Michelle M. A. Fernando, Deborah S. Cunninghame Graham and Timothy J. Vyse ()
Additional contact information
Christopher A. Odhams: King’s College London
Amy L. Roberts: 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
Samuel J. Daffern: King’s College London
Antonino Zito: King’s College London
Lingyan Chen: King’s College London
Leonardo L. Jones: King’s College London
Lora Boteva: King’s College London
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

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10106-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10106-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10106-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().