title: Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells.
abstract: OBJECTIVE
  To determine the effects of rapamycin on experimental autoimmune uveoretinitis (EAU) and investigate of role of rapamycin on T cell subsets in the disease.
  
  
  METHODS
  EAU was induced in rats using peptides 1169 to 1191 of the interphotoreceptor binding protein (IRBP). Rapamycin (0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6 produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4+CD25+ regulatory T cells (Tregs) from rat spleen were detected by flow cytometry.
  
  
  RESULTS
  Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro. Rapamycin also significantly increased TGF-β1 production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore, rapamycin decreased the ratio of Th17 cells/CD4+T cells and upregulated Tregs in EAU, as detected by flow cytometry.
  
  
  CONCLUSIONS
  Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU. Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China ; Hebei Eye Hospital, Xingtai 054001, Hebei Province, China.
authors: Li-Fei
authors: LF
authors: Yuan
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China ; Linyi People's Hospital, Linyi 276000, Shandong Province, China.
authors: Guang-Da
authors: GD
authors: Li
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China.
authors: Xin-Jun
authors: XJ
authors: Ren
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China.
authors: Hong
authors: H
authors: Nian
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China.
authors: Xiao-Rong
authors: XR
authors: Li
authors: Tianjin Medical University Eye Hospital & Eye Institute, Tianjin 300384, China.
authors: Xiao-Min
authors: XM
authors: Zhang
keywords: Th1 cells; Th17 cells; Th2 cells; experimental autoimmune uveoretinitis; rapamycin; regulatory T cells; uveitis