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

Hum Immunol. 2015 May;76(5):307-17. doi: 10.1016/j.humimm.2015.03.010. Epub 2015 Mar 19.

Abstract

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.

Keywords: CCR7; Dendritic cells; Maturation; MicroRNA; Promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Differentiation* / genetics
  • Dendritic Cells / immunology*
  • Gene Expression Regulation / immunology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Sp3 Transcription Factor / genetics
  • Sp3 Transcription Factor / metabolism

Substances

  • 3' Untranslated Regions
  • CCR7 protein, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • NFATC Transcription Factors
  • Receptors, CCR7
  • SP3 protein, human
  • Sp1 Transcription Factor
  • SP1 protein, human
  • mirnlet7 microRNA, human
  • Sp3 Transcription Factor