title: Mesenchymal stem cells ameliorate experimental autoimmune uveoretinitis by comprehensive modulation of systemic autoimmunity.
abstract: OBJECTIVE
  The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP).
  
  
  METHODS
  The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected.
  
  
  RESULTS
  MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells.
  
  
  CONCLUSIONS
  These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
authors.affiliation: Tianjin Medical University Eye Center, Tianjin, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xinjun
authors.initials: X
authors.lastname: Ren
authors.forename: Guangda
authors.initials: G
authors.lastname: Li
authors.forename: Chunna
authors.initials: C
authors.lastname: Jiao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Shaozhen
authors.initials: S
authors.lastname: Zhao
authors.forename: Jiantao
authors.initials: J
authors.lastname: Wang
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010446:Peptide Fragments; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C500522:Foxp3 protein, rat