title: Liver microRNA Profile of Induced Allograft Tolerance.
abstract: BACKGROUND
  Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total lymphoid irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance.
  
  
  METHODS
  To identify the miRNAs associated with TLI-induced tolerance, we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (Dark Agouti→Lewis) of orthotropic liver transplants that received posttransplant TLI, allogeneic recipients that were not treated posttransplantation and experienced acute rejection, and native Dark Agouti livers. Quantitative-polymerase chain reaction miRNA array cards were used to profile liver grafts.
  
  
  RESULTS
  We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared with syngeneic livers, with 80% of the miRNAs increased. In established tolerance, 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared with syngeneic livers. A principal component analysis of all miRNAs assayed demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers.
  
  
  CONCLUSIONS
  The miRNA profile of established tolerant allografts is very similar to syngeneic grafts, suggesting tolerance may be a return to an immunological state of quiescence.
authors.affiliation: 1 Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA. 2 School of Medicine, Sichuan Provincial People's Hospital, Chengdu, China. 3 Cleveland Clinic, Cleveland, OH. 4 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Matthew James
authors.initials: MJ
authors.lastname: Vitalone
authors.forename: Liang
authors.initials: L
authors.lastname: Wei
authors.forename: Masato
authors.initials: M
authors.lastname: Fujiki
authors.forename: Audrey H
authors.initials: AH
authors.lastname: Lau
authors.forename: Erik
authors.initials: E
authors.lastname: Littau
authors.forename: Carlos
authors.initials: C
authors.lastname: Esquivel
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Martinez
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Krams
mesh_terms: D064591:Allografts; D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006085:Graft Survival / Q000235:genetics; D000068884:Immunosenescence; D064596:Isografts; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D011917:Rats, Inbred Lew; D013997:Time Factors; D023001:Transplantation Tolerance / Q000235:genetics; D014185:Transplantation, Isogeneic
chemical_list: D035683:MicroRNAs