MiR-34a promotes DCs development and inhibits their function on T cell activation by targeting WNT1

Oncotarget. 2017 Mar 7;8(10):17191-17201. doi: 10.18632/oncotarget.15228.

Abstract

MicroRNAs serve important functions in numerous biological processes. Whether microRNAs also act on dendritic cell (DC) differentiation and function remains unclear. In this study, both conventional DCs (cDCs) and plasmacytoid DCs (pDCs) were increased in miR-34a overexpressing bone marrow chimeric and transgenic (TG) mice. Further experiments showed that miR-34a promoted preDC differentiated into cDCs and pDCs without affecting the proliferation and apoptosis of DCs. Luciferase report assay and Western blot experiments demonstrated that WNT1 is the direct target of miR-34a in DCs. Interestingly, miR-34a overexpressing cDCs also produced a large amount of IL-17a and suppressed T cell activation because of the inhibition of TCF1 expression, thus increasing RORγT expression. Taken together, miR-34a promotes preDC to differentiate into cDCs and pDCs, as well as inhibits the function of cDCs on the activation of CD4+ T cells by producing IL-17a.

Keywords: IL-17a; T cell activation; cDCs; development; miR-34a.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Lymphocyte Activation / genetics
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • T-Lymphocytes / metabolism*
  • Wnt1 Protein / genetics*
  • Wnt1 Protein / metabolism

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Interleukin-17
  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Wnt1 Protein