MicroRNA Profile of Circulating CD4-positive Regulatory T Cells in Human Adults and Impact of Differentially Expressed MicroRNAs on Expression of Two Genes Essential to Their Function.
In: Journal of Biological Chemistry, Jg. 287 (2012-03-23), Heft 13, S. 9910-9922
academicJournal
Zugriff:
Regulatory T cells (Tregs) are characterized by a high expression of IL-2 receptor α chain (CD25) and of forkhead box P3 (FOXP3), the latter being essential for their development and function. Another major player in the regulatory function is the cytotoxic T-lymphocyte associated molecule-4 (CTLA-4) that inhibits cytotoxic responses. However, the regulation of CTLA-4 expression remains less well explored. We therefore studied the microRNA signature of circulating CD4+ Tregs isolated from adult healthy donors and identified a signature composed of 15 differentially expressed microRNAs. Among those, miR-24, miR-145, and miR-210 were down-regulated in Tregs compared with controls and were found to have potential target sites in the 3'-UTR of FOXP3 and CTLA-4; miR-24 and miR-210 negatively regulated FOXP3 expression by directly binding to their two target sites in its 3'-UTR. On the other hand, miR-95, which is highly expressed in adult peripheral blood Tregs, positively regulated FOXP3 expression via an indirect mechanism yet to be identified. Finally, we showed that miR-145 negatively regulated CTLA-4 expression in human CD4+ adult peripheral blood Tregs by binding to its target site in CTLA-4 transcript 3'-UTR. To our knowledge, this is the first identification of a human adult peripheral blood CD4+ Treg microRNA signature. Moreover, unveiling one mechanism regulating CTLA-4 expression is novel and may lead to a better understanding of the regulation of this crucial gene. [ABSTRACT FROM AUTHOR]
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MicroRNA Profile of Circulating CD4-positive Regulatory T Cells in Human Adults and Impact of Differentially Expressed MicroRNAs on Expression of Two Genes Essential to Their Function.
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Autor/in / Beteiligte Person: | Fayyad-Kazan, Hussein ; Rouas, Redouane ; Fayyad-Kazan, Mohammad ; Badran, Rabih ; Zein, Nabil El ; Lewalle, Philippe ; Najar, Medhi ; Hamade, Eva ; Jebbawi, Fadi ; Merimi, Makram ; Romero, Pedro ; Burny, Arsène ; Badran, Bassam ; Martiat, Philippe |
Zeitschrift: | Journal of Biological Chemistry, Jg. 287 (2012-03-23), Heft 13, S. 9910-9922 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.M111.337154 |
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