title: Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression.
abstract: Treg are the main mediators of dominant tolerance. Their mechanisms of action and applications are subjects of considerable debate currently. However, a human microRNA (miR) Treg signature has not been described yet. We investigated human natural Treg and identified a signature composed of five miR (21, 31, 125a, 181c and 374). Among those, two were considerably under-expressed (miR-31 and miR-125a). We identified a functional target sequence for miR-31 in the 3' untranslated region (3' UTR) of FOXP3 mRNA. Using lentiviral transduction of fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had an effect on FOXP3 expression levels. We showed that miR-31 negatively regulates FOXP3 expression by binding directly to its potential target site in the 3' UTR of FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though indirect, regulator of FOXP3 expression. Transduction of the remaining three miR had no direct effect on FOXP3 expression or on the phenotype and will remain the subject of future investigations. In conclusion, not only have we identified and validated a miR signature for human natural Treg, but also unveiled some of the mechanisms by which this signature was related to the control of FOXP3 expression in these cells.
authors.affiliation: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Redouane
authors.initials: R
authors.lastname: Rouas
authors.forename: Hussein
authors.initials: H
authors.lastname: Fayyad-Kazan
authors.forename: Nabil
authors.initials: N
authors.lastname: El Zein
authors.forename: Philippe
authors.initials: P
authors.lastname: Lewalle
authors.forename: Françoise
authors.initials: F
authors.lastname: Rothé
authors.forename: Alexandru
authors.initials: A
authors.lastname: Simion
authors.forename: Haidar
authors.initials: H
authors.lastname: Akl
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mourtada
authors.forename: Mohamad
authors.initials: M
authors.lastname: El Rifai
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Philippe
authors.initials: P
authors.lastname: Martiat
authors.forename: Bassam
authors.initials: B
authors.lastname: Badran
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D020413:3' Untranslated Regions; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C524940:MIRN21 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense