title: Effect of CD40 silenced dendritic cells by RNA interference on mice skin allograft rejection.
abstract: OBJECTIVE
  Tolerogenic dendritic cells (DCs) play a critical role in inducing and maintaining tolerance. CD40 is a member of tumor necrosis factor receptor super family and is a potent T-cell costimulatory molecule. Therefore, in this study we evaluated the effect of CD40 silenced DCs by RNA interference on mice skin allograft rejection.
  
  
  METHODS
  Skin transplantation was performed from C57BL/6 to BALB/c mouse. Skin allograft recipients were assigned to four groups (n = 5). CD40 downregulated DCs were injected to the BALB/c mice intravenously 7 days before transplantation. Then, graft survival time, Treg generation, CD4(+) and CD8(+) T cells infiltration and cytokine levels in serum of this group were compared with those of untreated and cyclosporine groups.
  
  
  RESULTS
  In comparison with untreated group, BALB/c mice injected with CD40 siRNA transfected DCs showed an increased graft survival time, Treg cells, IL-4 and IL-10 cytokine levels as well as decreased number of intragraft CD4(+) and CD8(+) T cells. IFN-γ and IL-12 secretion were diminished, too.
  
  
  CONCLUSIONS
  Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Karimi
authors.forename: Saeed
authors.initials: S
authors.lastname: Marzban
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Hajiyan
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Rajabiyan
authors.forename: Salimeh
authors.initials: S
authors.lastname: Ebrahimnezhad
mesh_terms: D064591:Allografts; D000818:Animals; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D019013:CD40 Antigens; D016207:Cytokines
keywords: CD40; Treg; allograft rejection; dendritic cell; siRNA; skin transplantation; tolerance induction