Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility

Authors

  • Julie Tellier,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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    • These authors contributed equally to this work.

  • Andry Andrianjaka,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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    • These authors contributed equally to this work.

  • Rita Vicente,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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  • Nicolas Thiault,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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  • Geneviève Enault,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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  • Henri-Jean Garchon,

    1. Inserm U1016, Université Paris Descartes, Paris, France
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  • Joost P. M. van Meerwijk,

    1. Inserm, U1043, Toulouse, France
    2. CNRS, U5282, Toulouse, France
    3. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
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  • Paola Romagnoli

    Corresponding author
    1. CNRS, U5282, Toulouse, France
    2. Universitè de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
    • Inserm, U1043, Toulouse, France
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Full correspondence Dr. Paola Romagnoli, Inserm U1043, BP 3028, 31024 Toulouse Cedex 3, France

Fax: +33-562 744558

e-mail: Paola.Romagnoli@inserm.fr

Abstract

Regulatory T (Treg) lymphocytes play a central role in the control of autoimmune pathology. Any alteration in Treg-cell biology in mouse strains used for the study of these disorders therefore raises the question of its direct link with disease susceptibility. Paradoxically, in non-obese diabetic (NOD) mice increased numbers of Treg cells develop in the thymus. In this report we identify a locus of <7 Mbp that quantitatively controls Treg-cell development in the thymus of the NOD mouse. This ‘Trd1' region is located centromeric to the H2 complex on chromosome 17 and does not include genes encoding classical MHC molecules. The genomic region identified here contains the Idd16 diabetes susceptibility locus and the use of congenic mouse strains allowed us to investigate the potential link between quantitatively altered thymic Treg cells and diabetes susceptibility. Hybrid mice present similar levels of thymic Treg cells as B6 animals but they developed diabetes with the same kinetics as NOD mice. Therefore, the increased Treg-cell development in NOD mice controlled by Trd1 is functionally dissociated from the susceptibility of NOD to diabetes.

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