Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis

Authors

  • Laura Piccio,

    Corresponding author
    • Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
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  • Claudia Cantoni,

    1. Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
    2. Neurology Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Cá Granda, Ospedale Maggiore Policlinico, Milano, Italy
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  • Jacob G. Henderson,

    1. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA
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  • Daniel Hawiger,

    1. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA
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  • Michael Ramsbottom,

    1. Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
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  • Robert Mikesell,

    1. Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
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  • Jiyoon Ryu,

    1. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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  • Chyi-Song Hsieh,

    1. Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, USA
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  • Viviana Cremasco,

    1. Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA
    Current affiliation:
    1. Dana-Farber Cancer Institute, Boston, MA, USA
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  • Wesley Haynes,

    1. Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
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  • Lily Q. Dong,

    1. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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  • Lawrence Chan,

    1. Division of Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA
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  • Daniela Galimberti,

    1. Neurology Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Cá Granda, Ospedale Maggiore Policlinico, Milano, Italy
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  • Anne H. Cross

    1. Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
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Full correspondence Dr. Laura Piccio, Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA

Fax: +1-314-747-1345

e-mail: picciol@neuro.wustl.edu

Abstract

Multiple sclerosis (MS) is a presumed autoimmune disease directed against central nervous system (CNS) myelin, in which diet and obesity are implicated as risk factors. Immune responses can be influenced by molecules produced by fat cells, called adipokines. Adiponectin is an adipokine with anti-inflammatory effects. We tested the hypothesis that adiponectin has a protective role in the EAE model for MS, that can be induced by immunization with myelin antigens or transfer of myelin-specific T lymphocytes. Adiponectin deficient (ADPKO) mice developed worse EAE with greater CNS inflammation, demyelination, and axon injury. Lymphocytes from myelin-immunized ADPKO mice proliferated more, produced higher amounts of IFN-γ, IL-17, TNF-α, IL-6, and transferred more severe EAE than wild type (WT) lymphocytes. At EAE peak, the spleen and CNS of ADPKO had fewer regulatory T (Treg) cells than WT mice and during EAE recovery, Foxp3, IL-10 and TGF-β expression levels in the CNS were reduced in ADPKO compared with WT mice. Treatment with globular adiponectin in vivo ameliorated EAE, and was associated with an increase in Treg cells. These data indicate that adiponectin is an important regulator of T-cell functions during EAE, suggesting a new avenue of investigation for MS treatment.

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