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Genetic control of HgCl2-induced IgE and autoimmunity by a 117-kb interval on rat chromosome 9 through CD4 CD45RChigh T cells

Genes & Immunity volume 14, pages 258–267 (2013)Cite this article

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Abstract

Gold or mercury salts trigger a dramatic IgE response and a CD4 T-cell-dependent nephropathy in Brown-Norway (BN), but not in Lewis (LEW) rats. We previously identified the 1.1-Mb Iresp3 (immunoglobin response QTL3) locus on chromosome 9 that controls these gold salt-triggered immune disorders. In the present work, we investigated the genetic control of HgCl2-induced immunological disorders and assessed the relative contribution of the CD45RChigh and CD45RClow CD4 T-cell subpopulations in this control. By using interval-specific congenic lines, we narrowed down Iresp3 locus to 117-kb and showed that BN rats congenic for the LEW 117-kb were protected from HgCl2-triggered IgE response and nephropathy. This 117-kb interval also controls CD45RC expression by CD4 T cells and the ability of CD45RChigh CD4 T cells to trigger the autoimmune disorders resulting from HgCl2 administration. This 117-kb region contains four genes, including Vav1, a strong candidate gene according to its cellular function and exclusive expression in hematopoietic cells. Thus, this study highlights the role of the CD45RChigh CD4 T-cell subpopulation in the opposite susceptibility of BN and LEW rats to HgCl2-triggered immune disorders and identifies a 117-kb interval on chromosome 9 that has a key role in their functions.

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Acknowledgements

We would like to thank Daniel Dunia, Anne S Dejean and Philippe Druet for their critical comments on the manuscript. We would also like to thank Fatima L’Faqihi, Valérie Duplan-Eche and Delphine Lestrade from the flow-cytometry core facility (CPTP), the animal house staff members and the histopathology core facility for their technical assistance (UMS 06). This work was supported by INSERM, the Arthritis Fondation Courtin, Association Française contre les Myopathies, Agence Nationale de la Recherche (ANR-08-GENO-041-01), Association de Recherche sur la Sclérose En Plaques, Région Midi-Pyrénées and Fight-MG (FP7-Health-2009-242210). CP is supported by grants from Ministère de l'Education Nationale, de la Recherche et de la Technologie and from Fondation pour la Recherche Médicale. AS is supported by the Centre National de la Recherche Scientifique GJF, IB and DL by INSERM.

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Author notes

  1. V Garcia

    Present address: 6Present address: Centre Hospitalier de l'Université de Montréal, Hôpital Saint Luc, Service de Gynécologie Obstétrique, 1058, Rue St Denis, Montréal, Québec H2X 3J4, Canada.,

  2. C Pedros and O Papapietro: These authors contributed equally to this work.

  3. G J Fournié and A Saoudi: These authors codirected this work.

Authors and Affiliations

  1. UMR Inserm, U1043, Toulouse, France

    C Pedros, O Papapietro, C Colacios, A Casemayou, I Bernard, V Garcia, D Lagrange, B Mariamé, G J Fournié & A Saoudi

  2. UMR CNRS, U5282, Toulouse, France

    C Pedros, O Papapietro, C Colacios, A Casemayou, I Bernard, V Garcia, D Lagrange, B Mariamé, G J Fournié & A Saoudi

  3. Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France

    C Pedros, O Papapietro, C Colacios, A Casemayou, I Bernard, V Garcia, D Lagrange, B Mariamé, G J Fournié & A Saoudi

  4. UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

    O Andreoletti

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CP, OP, CC, AS and GJF conceived and designed the experiments. CP, OP, CC, AC, IB, VG, DL, BM and OA performed the experiments. CP OP, CC, IB and OA analyzed the data. CP, OP, CC, GJF and AS wrote the paper. GJF and AS supervised overall project.

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Pedros, C., Papapietro, O., Colacios, C. et al. Genetic control of HgCl2-induced IgE and autoimmunity by a 117-kb interval on rat chromosome 9 through CD4 CD45RChigh T cells. Genes Immun 14, 258–267 (2013). https://doi.org/10.1038/gene.2013.21

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