title: Human mesenchymal stem cells upregulate CD1dCD5(+) regulatory B cells in experimental autoimmune encephalomyelitis.
abstract: OBJECTIVE
  Multiple sclerosis (MS) causes significant neurological disability. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Human bone marrow mesenchymal stem cells (hMSCs) possess anti-inflammatory and immunosuppressive effects. We studied whether hMSCs affect CD1d(high)CD5(+) regulatory B-cell activity in EAE.
  
  
  METHODS
  EAE was induced in C57BL/6N mice by immunization with MOG35-55 peptide. hMSCs were injected intravenously into EAE mice on day 3 and day 12 after first immunization. Mice were sacrificed on day 26. Immunohistochemistry of the spinal cord, serum cytokines levels, production of cytokines by cultured splenic cells, and flow cytometry for splenic Th17 and CD1d(high)CD5(+) regulatory B cells were studied.
  
  
  RESULTS
  EAE mice with hMSC treatment on day 3 and day 12 had reduced EAE scores from day 14 to day 26 compared to EAE mice without hMSC treatment, and reduced infiltration of inflammatory cells and demyelination in the spinal cord. EAE mice with hMSC treatment on day 3 and day 12 had: (1) lower serum levels of IL-6, TNF-α (p < 0.0005), and IL-17 (p < 0.005 for day 3, p < 0.0005 for day 12); (2) reduced splenic cell production and secretion of IL-6, TNF-α (p < 0.05), and IL-17 (p < 0.05), and increased splenic production of IL-10; (3) reduced splenic Th17 cells (p < 0.05 for day 3, p < 0.005 for day 12), and (4) increased CD1d(high)CD5(+) regulatory B cells (p < 0.005) compared to EAE mice without hMSC treatment.
  
  
  CONCLUSIONS
  hMSC treatment on day 3 and day 12 suppresses EAE severity. The underlying mechanisms involve downregulation of Th17 cells and upregulation of CD1d(high)CD5(+) regulatory B-cell activity.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, Hong Kong, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Guo
authors.forename: Koon-Ho
authors.initials: KH
authors.lastname: Chan
authors.forename: Wing-Hon
authors.initials: WH
authors.lastname: Lai
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Shing-Cheong
authors.initials: SC
authors.lastname: Kwan
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Philip
authors.initials: P
authors.lastname: Wing-Lok Ho
authors.forename: Jessica
authors.initials: J
authors.lastname: Wing-Man Ho
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D018956:CD5 Antigens / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000601:surgery*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D055610:Antigens, CD1d; D018956:CD5 Antigens; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55)