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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
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
An essential role for Scurfin in CD4+CD25+ T regulatory cells
Khattri, R., Cox, T., Yasayko, S.-A., & Ramsdell, F. (2003) · Nature Immunology · doi:10.1038/ni909 · Cited by 2,860
MacLennan, I. C. M. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.001001 · Cited by 1,795
Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Zheng, N., Schulman, B. A., Song, L., Miller, J. J., Jeffrey, P. D., Wang, P., Chu, C., Koepp, D. M., Elledge, S. J., Pagano, M., et al. (2002) · Nature · doi:10.1038/416703a · Cited by 1,507
ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28
Hutloff, A., Dittrich, A. M., Beier, K. C., Eljaschewitsch, B., Kraft, R., Anagnostopoulos, I., & Kroczek, R. A. (1999) · Nature · doi:10.1038/16717 · Cited by 1,482
Parrish-Novak, J. E., Dillon, S. R., Nelson, A., Hammond, A., Sprecher, C. A., Gross, J. A., Johnston, J. V., Madden, K., Xu, W., West, J., et al. (2000) · Nature · doi:10.1038/35040504 · Cited by 1,222
Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo.
Kearney, E. R., Pape, K., Loh, D., & Jenkins, M. (1994) · Immunity · doi:10.1016/1074-7613(94)90084-1 · Cited by 1,126
A Critical Role for IL-21 in Regulating Immunoglobulin Production
Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., Liu, C., Schwartzberg, P. L., & Leonard, W. J. (2002) · Science · doi:10.1126/science.1077002 · Cited by 978
ICOS co-stimulatory receptor is essential for T-cell activation and function
Dong, C., Juedes, A. E., Temann, U.-A., Shresta, S., Allison, J. P., Ruddle, N. H., & Flavell, R. A. (2001) · Nature · doi:10.1038/35051100 · Cited by 929
Structure of a c-Cbl–UbcH7 Complex
Zheng, N., Wang, P., Jeffrey, P. D., & Pavletich, N. P. (2000) · Cell · doi:10.1016/s0092-8674(00)00057-x · Cited by 839
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Chen, Y., Atnerkar, A., & Yu, D. (2016) · Wiley eBooks · doi:10.1002/9780470015902.a0024155
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Xie, M. M. (2019) · IUScholarWorks (Indiana University) · doi:10.7912/c2/1758
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Potter, P. K. (2018) · Wiley eBooks · doi:10.1002/9780470015902.a0022409.pub2
Siqueira, R. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2019.tde-02102019-143339
Rodríguez‐Rodríguez, N., Rosetti, F., & Crispín, J. C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801917-7.00013-9
ICOS (Inducible T-Cell Costimulatory) Deficiency (OMIM # 607594)
Kobrynski, L. J. (2017) · Springer eBooks · doi:10.1007/978-1-4614-9209-2_86-1
Genome-Wide Mutagenesis in Mice: In Search for Genes Regulating Immune Responses and Inflammation
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Olson, W. J., Jakic, B., Labi, V., Schoeler, K., Kind, M., Klepsch, V., Baier, G., & Hermann‐Kleiter, N. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3357921
Silva (2017) · Digital Repository Service (Northeastern University) · doi:10.17760/d20284697
Nakandakari-Higa, S., & Jacobsen, J. T. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1736-6_2
Faculty Opinions recommendation of Follicular helper T cells are required for systemic autoimmunity.
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Snow, E. C. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13093957.14653169
Blazar, B. R., & Bucher, C. M. (2009) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1148074.605187
Diamond, B., & Grimaldi, C. M. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-3285-4.10010-5
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Salzer, U. (2018) · Rare diseases of the immune system · doi:10.1007/978-3-319-91785-6_6
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Lu, W., Zhou, M., Wang, B., Liu, X., & Li, B. (2020) · Figshare · doi:10.6084/m9.figshare.13279230
Crispín, J. C., Kono, M., & Tsokos, G. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-93232-5.00020-4
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Hirsch, E. S., Brimmer, K. E., & Weinstein, J. S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00281-7
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Attridge, K. (2012) · University of Birmingham Institutional Research Archive (University of Birmingham)
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Veber, R. (2018) · theses.fr (ABES) · doi:10.70675/cdc0e39czbb69z48eaz8281z13f8ffb581dd
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Kang, S., Kim, D. E., Kim, N. D., Eunju, O., Yoon, H. J., Joo, Y., Hong, S., & Kim, K. S. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01756-6
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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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