Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis |
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Authors: | Laura Piccio Claudia Cantoni Jacob G. Henderson Daniel Hawiger Michael Ramsbottom Robert Mikesell Jiyoon Ryu Chyi‐Song Hsieh Viviana Cremasco Wesley Haynes Lily Q. Dong Lawrence Chan Daniela Galimberti Anne H. Cross |
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Affiliation: | 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;3. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, , St. Louis, MO, USA;4. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, , San Antonio, TX, USA;5. Department of Medicine, Division of Rheumatology, Washington University School of Medicine, , St. Louis, MO, USA;6. Department of Orthopedics, Washington University School of Medicine, , St. Louis, MO, USA;7. Division of Endocrinology and Metabolism, Baylor College of Medicine, , Houston, TX, USA |
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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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Keywords: | Adiponectin EAE Immunomodulation Multiple sclerosis |
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