title: Differential profile of activated regulatory T cell subsets and microRNAs in tolerant liver transplant recipients.
abstract: Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplantation (LT) patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on LT tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) LT recipients by cellular, genetic, and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the forkhead box P3 (FOXP3) regulatory T cell-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs. Tol patients presented a different signature of Treg subset markers compared with non-Tol patients with increased expression of HELIOS and FOXP3 and a higher proportion of latency-associated peptide (LAP)+Tregs and CD45RA-human leukocyte antigen D related (HLA-DR)+activated effector-memory Tregs. The expression of miR95, miR24, miR31, miR146a, and miR155 was higher in Tol than in non-Tol patients and was positively correlated with activated Treg markers. In conclusion, these data suggest that activated effector-memory Tregs and a TSDR-demethylation state of Tregs may play a role in the complex system of regulation of LT tolerance. In addition, we describe a set of miRNAs differentially expressed in human LT Tol patients providing suggestive evidence that miRNAs are implied in the preservation of self-tolerance as mediated by Tregs. Liver Transplantation 23 933-945 2017 AASLD.
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Revilla-Nuin
authors.affiliation: Clinical Laboratory Unit, Hospital General Universitario Santa Lucía, Cartagena, Spain.
authors.forename: África
authors.initials: Á
authors.lastname: de Bejar
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Martínez-Alarcón
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Pamplona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Herrero
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.
authors.forename: Carlos Manuel
authors.initials: CM
authors.lastname: Martínez-Cáceres
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.|Division of Gastroenterology and Hepatology and Liver Transplant Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ramírez
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Baroja-Mazo
authors.affiliation: Biomedical Research Institute of Murcia, University Clinical Hospital "Virgen de la Arrixaca," University of Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Murcia, Spain.|Division of Gastroenterology and Hepatology and Liver Transplant Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Pons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D000073398:Demethylation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000502:physiology; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D035683:MicroRNAs