CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice

Authors

  • Jun-Qi Yang,

    1. Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, USA
    2. Veterans Affairs Medical Center, Cincinnati, USA
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    • The first two authors contributed equally to the work.

  • Taehoon Chun,

    1. Gwen Knapp Center, University of Chicago, Chicago, USA
    2. Present addresses Hanyang University, School of Medicine, Department of Microbiology, Seoul 133–791, South Korea
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  • Hongzhu Liu,

    1. Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, USA
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  • Seokmann Hong,

    1. Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, USA
    2. Department of Bioscience and Biotechnology, Sejong University, Seoul 143–747, South Korea
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  • Hai Bui,

    1. Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, USA
    2. Veterans Affairs Medical Center, Cincinnati, USA
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  • Luc Van Kaer,

    1. Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, USA
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  • Chyung-Ru Wang,

    1. Gwen Knapp Center, University of Chicago, Chicago, USA
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  • Ram Raj Singh

    Corresponding author
    1. Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, USA
    2. Veterans Affairs Medical Center, Cincinnati, USA
    • MSB 7464, 231 Albert Sabin Way, University of Cincinnati College of Medicine, Cincinnati, OH 45267–0563, USA Fax: +1-513–558–3799
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Abstract

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have establishedMRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4+ T cells in the spleen and liver and of TCRα β +B220+ cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.

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