title: Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis.
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.
authors: Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA. picciol@neuro.wustl.edu
authors: Laura
authors: L
authors: Piccio
authors: Claudia
authors: C
authors: Cantoni
authors: Jacob G
authors: JG
authors: Henderson
authors: Daniel
authors: D
authors: Hawiger
authors: Michael
authors: M
authors: Ramsbottom
authors: Robert
authors: R
authors: Mikesell
authors: Jiyoon
authors: J
authors: Ryu
authors: Chyi-Song
authors: CS
authors: Hsieh
authors: Viviana
authors: V
authors: Cremasco
authors: Wesley
authors: W
authors: Haynes
authors: Lily Q
authors: LQ
authors: Dong
authors: Lawrence
authors: L
authors: Chan
authors: Daniela
authors: D
authors: Galimberti
authors: Anne H
authors: AH
authors: Cross
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D012307:Risk Factors; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Adiponectin; EAE; Immunomodulation; Multiple sclerosis
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