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NFAT-1, Sp-1, Sp-3, and miR-21: New regulators of chemokine C receptor 7 expression in mature human dendritic cells

par Al-Akoum, Carine;Badran, Bassam ;Akl, Israa ;Rouas, Redouane ;Fayyad Kazan, Mohammad ;Falha, Layal;Renno, Toufic;Burny, Arsène ;Lewalle, Philippe ;Fayyad Kazan, Hussein
Référence Human immunology, 76, 5, page (307-317)
Publication Publié, 2015-05

Article révisé par les pairs

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Résumé :

The chemokine C receptor 7 (CCR7) is a G-protein-coupled heptahelical receptor (GPCR) that is expressed on a wide variety of cells including memory T cells, B cells, mature dendritic cells, and cancer cells. Activated by its ligands CCL19 or CCL21, CCR7 plays a major role in metastasis of cancer cells. Recent studies demonstrated the role of NF-κB and AP-1 transcription factors in addition to let-7 microRNA in CCR7 expression. Our ChIP assays further show the binding of Sp-1, Sp-3 and NFAT-1 transcription factors to their potential binding sites in the 1Kb promoter region with the later found to inhibit whilst Sp-1, and Sp-3 were found to stimulate CCR7 expression as demonstrated by transfection assays. On the other hand, in addition to the known let-7 regulation of CCR7, we found miR-21 to have a highly conserved target region in CCR7 3'UTR and to be significantly down-regulated during the course of dendritic cell maturation, allowing for high expression of CCR7.