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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2089-2100
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Adiponectin
  • EAE
  • Immunomodulation
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Piccio, L., Cantoni, C., Henderson, J. G., Hawiger, D., Ramsbottom, M., Mikesell, R., Ryu, J., Hsieh, C. S., Cremasco, V., Haynes, W., Dong, L. Q., Chan, L., Galimberti, D., & Cross, A. H. (2013). Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis. European Journal of Immunology, 43(8), 2089-2100. https://doi.org/10.1002/eji.201242836