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Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation

Vogel, Katharina U (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Edelmann, Stephanie L (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Jeltsch, Katharina M (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
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Bertossi, Arianna (author)
Max Planck Institute of Biochemistry, Martinsried, Germany
Heger, Klaus (author)
Max Planck Institute of Biochemistry, Martinsried, Germany
Heinz, Gitta A (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Zöller, Jessica (author)
Institute for Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
Warth, Sebastian C (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Hoefig, Kai P (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Lohs, Claudia (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Neff, Frauke (author)
Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany
Kremmer, Elisabeth (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
Schick, Joel (author)
Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
Repsilber, Dirk, 1971- (author)
Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany
Geerlof, Arie (author)
Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany
Blum, Helmut (author)
Laboratory for Functional Genome Analysis, Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany
Wurst, Wolfgang (author)
Institute of PAthology, Helmholtz Zentrum München, Neuherberg, Germany; Max-Planck-Institute of Psychiatry, Munich, Germany; Technische Universität München, Lehrstuhl für Entwicklungsgenetik c/o Helmholtz Zentrum München, Neuherberg, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Munich, Germany
Heikenwälder, Mathias (author)
Institute for Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
Schmidt-Supprian, Marc (author)
Max Planck Institute of Biochemistry, Martinsried, Germany
Heissmeyer, Vigo (author)
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany; Institute for Immunology, Ludwig-Maximilians-Universität München, Munich, Germany
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 (creator_code:org_t)
Cambridge, USA : Cell Press, 2013
2013
English.
In: Immunity. - Cambridge, USA : Cell Press. - 1074-7613 .- 1097-4180. ; 38:4, s. 655-68
Related links:
http://www.cell.com/...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The Roquin-1 protein binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. A single point mutation in Roquin-1, but not gene ablation, increases follicular helper T (Tfh) cell numbers and causes lupus-like autoimmune disease in mice. In T cells, we did not identify a unique role for the much lower expressed paralog Roquin-2. However, combined ablation of both genes induced accumulation of T cells with an effector and follicular helper phenotype. We showed that Roquin-1 and Roquin-2 proteins redundantly repressed the mRNA of inducible costimulator (Icos) and identified the Ox40 costimulatory receptor as another shared mRNA target. Combined acute deletion increased Ox40 signaling, as well as Irf4 expression, and imposed Tfh differentiation on CD4(+) T cells. These data imply that both proteins maintain tolerance by preventing inappropriate T cell activation and Tfh cell differentiation, and that Roquin-2 compensates in the absence of Roquin-1, but not in the presence of its mutated form.

Subject headings

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

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