Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression.
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.
Rouas
Redouane
R
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium.
Fayyad-Kazan
Hussein
H
El Zein
Nabil
N
Lewalle
Philippe
P
Rothé
Françoise
F
Simion
Alexandru
A
Akl
Haidar
H
Mourtada
Mohamad
M
El Rifai
Mohamad
M
Burny
Arsène
A
Romero
Pedro
P
Martiat
Philippe
P
Badran
Bassam
B
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
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