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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-05

AUTHORS

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, Christopher C. Goodnow

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. More... »

PAGES

452

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature03555

    DOI

    http://dx.doi.org/10.1038/nature03555

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013972387

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15917799


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