Decreased FOXP3 levels in multiple sclerosis patients

Authors

  • Jianya Huan,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
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  • Nicole Culbertson,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and OHSU, Portland, Oregon
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  • Leslie Spencer,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and OHSU, Portland, Oregon
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  • Richard Bartholomew,

    1. The Immune Response Corporation, Carlsbad, California
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  • Gregory G. Burrows,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Department of Biochemistry and Molecular Biology, Oregon Health and Science University,Portland, Oregon
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  • Yuan K. Chou,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and OHSU, Portland, Oregon
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  • Dennis Bourdette,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
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  • Steven F. Ziegler,

    1. Benaroya Research Institute, Seattle, Washington
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  • Halina Offner,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and OHSU, Portland, Oregon
    3. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon
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  • Arthur A. Vandenbark

    Corresponding author
    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon
    2. Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and OHSU, Portland, Oregon
    3. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon
    • Neuroimmunology Research R&D-31, VA Medical Center, Portland, OR 97201
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  • A.A.V. has a significant financial interest in The Immune Response Corporation, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU and VAMC Conflict of Interest Committees.

Abstract

Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is the first to establish that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4+CD25+ T cells (Tregs) that are quantitatively related to a reduction in functional suppression induced during suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links a defect in functional peripheral immunoregulation to an established genetic marker that has been unequivocally shown to be involved in maintaining immune tolerance and preventing autoimmune diseases. Diminished FOXP3 levels thus indicate impaired immunoregulation by Tregs that may contribute to MS. Future studies will evaluate the effects of therapies known to influence Treg cell function and FOXP3 expression, including TCR peptide vaccination and supplemental estrogen. © 2005 Wiley-Liss, Inc.

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