title: Semi-mature MyD88-silenced bone marrow dendritic cells prolong the allograft survival in a rat model of intestinal transplantation.
abstract: BACKGROUND
  Semi-mature dendritic cells (DCs) may induce tolerance rather than immunity. However, little is known about the regulatory mechanism by which these DCs induce transplant tolerance. Myeloid differentiation factor 88 (MyD88) is a key adaptor of Toll-like receptor signaling, which plays a critical role in DC maturation. Activation of MyD88-silenced immature DCs results in the generation of semi-mature DCs. We explored the possibility of using these DCs to induce intestinal transplant tolerance in rats.
  
  
  METHODS
  MyD88 expression was silenced in bone marrow DCs (F344 rats) using small interfering RNAs for 24 hours, at which point, lipopolysaccharide (LPS) was added to the culture for another 48 hours. These cells were analyzed for their in vitro and in vivo tolerizing capacities.
  
  
  RESULTS
  Semi-mature DCs expressing moderate levels of MHC class II and low levels of co-stimulatory molecules were found to produce interleukin (IL)-10, while IL-12 production was decreased. In vitro co-culture with completely allogeneic T cells from Wistar rats led to a significant decrease in alloreactive T-cell responses. In vivo, the transfer of semi-mature DCs (1 × 10(6) cells) followed by the transplantation of fully mismatched intestinal grafts (F344 rats) led to significantly prolonged survival compared to rats receiving immature and mature DCs. Serum from semi-mature DC-treated rats contained lower concentrations of the pro-inflammatory cytokines IL-2 and interferon-γ 5 days after transplantation.
  
  
  CONCLUSIONS
  Semi-mature DCs may promote inducible allograft tolerance and this study suggests a new strategy by which to facilitate the induction of transplant tolerance.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Yang
authors.forename: Song
authors.initials: S
authors.lastname: Meng
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Wen-Xi
authors.initials: WX
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007422:Intestines / Q000637:transplantation*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000378:metabolism; D014184:Transplantation, Homologous / Q000379:methods*
chemical_list: D053594:Myeloid Differentiation Factor 88