• Open Access

LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome

Authors

  • Iris Pinheiro,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
    3. Department of Plant Systems Biology, VIB, Ghent, Belgium
    4. Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium
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  • Lien Dejager,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Ioanna Petta,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Sofie Vandevyver,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Leen Puimège,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Tina Mahieu,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Marlies Ballegeer,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Filip Van Hauwermeiren,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Carlo Riccardi,

    1. Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia, Italy
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  • Marnik Vuylsteke,

    1. Department of Plant Systems Biology, VIB, Ghent, Belgium
    2. Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium
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  • Claude Libert

    Corresponding author
    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
    • Tel: +32-93313700; Fax: +32-93313609
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  • Iris Pinheiro and Lien Dejager share first authorship.

  • Marnik Vuylsteke and Claude Libert share senior authorship.

Abstract

Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis.

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