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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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
Journal of Biological Chemistry, Volume 287, No. 13, Year 2012
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Description
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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Fayyad-kazan, Hussein
Belgium, Brussels
Institut Jules Bordet
Rouas, Rédouane
Belgium, Brussels
Institut Jules Bordet
Fayyad-Kazan, Mohammad
Belgium, Brussels
Institut Jules Bordet
Badran, Rabih
Belgium, Brussels
Institut Jules Bordet
El-Zein, Nabil
Belgium, Brussels
Institut Jules Bordet
Lewalle, Philippe
Belgium, Brussels
Institut Jules Bordet
Najar, Mehdi
Belgium, Brussels
Institut Jules Bordet
Hamade, Eva
Lebanon, Beirut
Université Libanaise
Jebbawi, Fadi
Belgium, Brussels
Institut Jules Bordet
Merimi, Makram
Belgium, Brussels
Institut Jules Bordet
Romero, Pedro J.
Switzerland, Epalinges
Ludwig Institute for Cancer Research Lausanne
Burny, Arséne
Belgium, Brussels
Institut Jules Bordet
Badran, Bassam M.
Lebanon, Beirut
Université Libanaise
Martiat, Philippe
Belgium, Brussels
Institut Jules Bordet
Statistics
Citations: 89
Authors: 14
Affiliations: 3
Identifiers
Doi:
10.1074/jbc.M111.337154
ISSN:
00219258
e-ISSN:
1083351X
Research Areas
Genetics And Genomics