A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Carola G. Vinuesa (), Matthew C. Cook, Constanza Angelucci, Vicki Athanasopoulos, Lixin Rui, Kim M. Hill, Di Yu, Heather Domaschenz, Belinda Whittle, Teresa Lambe, Ian S. Roberts, Richard R. Copley, John I. Bell, Richard J. Cornall and Christopher C. Goodnow ()
Additional contact information
Carola G. Vinuesa: The Australian National University
Matthew C. Cook: The Australian National University Medical School
Constanza Angelucci: The Australian National University
Vicki Athanasopoulos: The Australian National University
Lixin Rui: The Australian National University
Kim M. Hill: The Australian National University
Di Yu: The Australian National University
Heather Domaschenz: The Australian National University
Belinda Whittle: The Australian National University
Teresa Lambe: University of Oxford
Ian S. Roberts: John Radcliffe Hospital
Richard R. Copley: University of Oxford
John I. Bell: University of Oxford
Richard J. Cornall: University of Oxford
Christopher C. Goodnow: The Australian National University

Nature, 2005, vol. 435, issue 7041, 452-458

Abstract: Abstract Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability.

Date: 2005
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature03555 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:435:y:2005:i:7041:d:10.1038_nature03555

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

DOI: 10.1038/nature03555

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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