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Differential profile of activated regulatory T cell subsets and microRNAs in tolerant liver transplant recipients
Author(s) -
RevillaNuin Beatriz,
de Bejar África,
MartínezAlarcón Laura,
Herrero José Ignacio,
MartínezCáceres Carlos Manuel,
Ramírez Pablo,
BarojaMazo Alberto,
Pons José Antonio
Publication year - 2017
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.24691
Subject(s) - foxp3 , immunology , microrna , liver transplantation , epigenetics , regulatory t cell , demethylation , medicine , effector , transplantation , cancer research , biology , t cell , gene , gene expression , il 2 receptor , genetics , immune system , dna methylation
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.