title: Immune tolerance induced by RelB short-hairpin RNA interference dendritic cells in liver transplantation.
abstract: BACKGROUND
  The induction of specific immune tolerance for alloantigen is the best method for solving transplant rejection. We have previously reported T-cell tolerance induced by RNA interference (RNAi) RelB dendritic cells (DCs), supporting the possibility of immunologic tolerance in liver transplantation.
  
  
  METHODS
  A stable model of acute rejection was established in Lewis (RT11) rats that had received a liver graft from dark agouti-RT1a rats. To evaluate the immune tolerance of DCs of different maturity, the rats were randomly assigned to four groups (12 donor/recipient pairs): (1) control-DC group, recipient rats without preinjection; (2) RelB short hairpin (sh)RNAi-DC group, recipient rats with preinjection of tolerogenic DCs by way of RelB silencing; (3) imDC group, recipient rats with preinjection of immature DCs; and (4) lipopolysaccharide-DC group, recipient rats with preinjection of mature DCs. The immune tolerance of the grafts was evaluated by liver function tests (aspartate transaminase, total bilirubin), cytokines (interleukin [IL]-2, IL-4, IL-10 and interferon-γ), and histopathologic examination during the 2 wk after transplantation. The survival time of the rats was also observed.
  
  
  RESULTS
  Compared with the other three groups, the graft survival time was significantly prolonged in the RelB shRNAi-DC group. In addition, RelB shRNAi-DCs resulted in the reduced secretion of IL-2 and interferon-γ and increased levels of IL-10 and IL-4. The symptoms of rejection were obviously alleviated in the RelB shRNAi-DC group, and the rejection activity index was still reduced after 2 wk.
  
  
  CONCLUSIONS
  Injection of RelB-silenced DCs contributed to the reduced incidence of graft rejection and prolonged the graft survival time. The potential mechanisms involved the regulation and induction of immune-incompetent T cell by DCs.
authors.affiliation: First Affiliated Hospital of Xinjiang Medical University, Urumqi, China; 23th Hospital of Chinese People's Liberation Army, Urumqi, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Bao
authors.forename: Yongge
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Zou
authors.forename: Zengjie
authors.initials: Z
authors.lastname: Tang
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Dong
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D006085:Graft Survival; D007108:Immune Tolerance; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D051841:Transcription Factor RelB / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; C497595:Relb protein, rat; D051841:Transcription Factor RelB