The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids

Nat Immunol. 2014 Jan;15(1):54-62. doi: 10.1038/ni.2767. Epub 2013 Nov 24.

Abstract

miR-126 is a microRNA expressed predominately by endothelial cells and controls angiogenesis. We found miR-126 was required for the innate response to pathogen-associated nucleic acids and that miR-126-deficient mice had greater susceptibility to infection with pseudotyped HIV. Profiling of miRNA indicated that miR-126 had high and specific expression by plasmacytoid dendritic cells (pDCs). Moreover, miR-126 controlled the survival and function of pDCs and regulated the expression of genes encoding molecules involved in the innate response, including Tlr7, Tlr9 and Nfkb1, as well as Kdr, which encodes the growth factor receptor VEGFR2. Deletion of Kdr in DCs resulted in reduced production of type I interferon, which supports the proposal of a role for VEGFR2 in miR-126 regulation of pDCs. Our studies identify the miR-126-VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Immunoblotting
  • Interferon-alpha / blood
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • MicroRNAs / metabolism
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / immunology
  • NF-kappa B p50 Subunit / metabolism
  • Nucleic Acids / immunology
  • Nucleic Acids / metabolism
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / immunology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Transcriptome / immunology
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Interferon-alpha
  • MIRN126 microRNA, mouse
  • MicroRNAs
  • NF-kappa B p50 Subunit
  • Nucleic Acids
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Nfkb1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2

Associated data

  • GEO/GSE51255