The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity
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.
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“Interestingly, RC3H1 also encodes a protein that has an amino-terminal RING-1 zinc-finger, which is characteristic to that of the E3 ubiquitin ligase family.50”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [50]
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Cites
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ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28
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A Critical Role for IL-21 in Regulating Immunoglobulin Production
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ICOS co-stimulatory receptor is essential for T-cell activation and function
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Follicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738
Victora, G. D., & Nussenzweig, M. C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075032 · Cited by 1,878
The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation
Ouyang, W., Kolls, J. K., & Zheng, Y. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.004 · Cited by 1,748
Johnston, R. J., Poholek, A. C., DiToro, D., Yusuf, I., Eto, D., Barnett, B., Dent, A. L., Craft, J., & Crotty, S. (2009) · Science · doi:10.1126/science.1175870 · Cited by 1,626
Morita, R., Schmitt, N., Bentebibel, S.-E., Ranganathan, R., Bourdery, L., Zurawski, G., Foucat, E., Dullaers, M., Oh, S., Sabzghabaei, N., et al. (2011) · Immunity · doi:10.1016/j.immuni.2010.12.012 · Cited by 1,563
Metadata
- Authors
- Vinuesa, C. G., Cook, M. C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K. M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., Roberts, I. S., Copley, R. R., Bell, J. I., Cornall, R. J., & Goodnow, C. C.
- Affiliations
- Australian National University (AU)
- University of Oxford (GB)
- John Radcliffe Hospital (GB)
- Centre for Human Genetics (GB)
- Corresponding author
- Vinuesa, Carola G.
- Goodnow, Christopher C.
- ORCID
- Venue
- Nature
- Published
- 2005-05
- Volume
- 435
- Issue
- 7041
- Pages
- 452-458
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2031622194
- Cited by
- 862
- References
- 50
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 28 · 2023: 21 · 2022: 24 · 2021: 46 · 2020: 33 · 2019: 50 · 2018: 43 · 2017: 34 · 2016: 61 · 2015: 54 · 2014: 60 · 2013: 64 · 2012: 50
- FWCI
- 14.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- Roquin, T follicular helper cells, germinal center, ICOS, IL-21, autoimmunity, lupus, diabetes mellitus, autoantibodies, self-tolerance, RNA granules, CCCH zinc finger, RNA-binding proteins, mRNA stability, T cell costimulation
- MeSH terms
- Amino Acid Sequence, Animals, Autoantibodies, Disease Models, Animal, Female, T-Lymphocytes, Helper-Inducer, Humans, Lupus Erythematosus, Systemic, Male, Molecular Sequence Data, Receptors, Antigen, T-Cell, Autoimmunity, Mutation, Missense, Ubiquitin-Protein Ligases, Cell Line, Tumor, Mice
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