title: PU.1-Silenced Dendritic Cells Induce Mixed Chimerism and Alleviate Intestinal Transplant Rejection in Rats via a Th1 to Th2 Shift.
abstract: OBJECTIVE
  Intestinal transplantation is an effective treatment for end-stage bowel failure; however, graft rejection and the toxicity associated with non-specific immunosuppression are major limitations of this procedure. Studies have shown that mixed chimerism can produce post-transplantation immune tolerance. Here, we demonstrate that in rat intestinal transplantation, PU.1-silenced dendritic cells (DCs) plus bone marrow (BM) cell transfusion results in mixed chimerism, and we investigate the mechanisms responsible for the effects of mixed chimerism rejection.
  
  
  METHODS
  In a model of intestinal transplantation, male Brown Norway rats were the donors, and female Lewis rats were the recipients that were randomly divided into 4 groups: control, BM, BM-imDCs and BM-PU.1. The dynamic changes in graft morphology, rejection scoring and serum concentrations of Th1/Th2-related cytokines were investigated on postoperative days 0, 7, 14, 21, and 30.
  
  
  RESULTS
  The BM-PU.1 group had better graft health, milder pathologic injuries, and lower rejection grades compared with the other groups. The rates of mixed chimerism were significantly highest in the BM-PU.1 group and correlated with decreases in serum IL-2 and increases in serum IL-10.
  
  
  CONCLUSIONS
  Transfusion of PU.1-silenced DCs and BM cells induces stable mixed chimerism and has the potential to reduce pathologic injuries via a pro-Th2 shift in the Th1/Th2 balance.
authors.affiliation: Jinling Hospital, Research Institute of General Surgery, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhao
authors.forename: Yannian
authors.initials: Y
authors.lastname: Liao
authors.forename: Wu
authors.initials: W
authors.lastname: Ji
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Li
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D046528:Chimerism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014184:Transplantation, Homologous; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D016753:Interleukin-10; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D051876:Sex-Determining Region Y Protein; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1