The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release

Immunity. 2013 Sep 19;39(3):521-36. doi: 10.1016/j.immuni.2013.08.035.

Abstract

NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / metabolism
  • Animals
  • Cells, Cultured
  • Crohn Disease / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Escherichia coli / immunology
  • Escherichia coli Infections / immunology
  • Humans
  • Inflammation / immunology
  • Interleukin-12 Subunit p40 / metabolism
  • Interleukin-23 / metabolism*
  • Intestinal Mucosa / immunology
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Polymorphism, Single Nucleotide
  • Th17 Cells / immunology

Substances

  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • MIRN29 microRNA, human
  • MicroRNAs
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein

Associated data

  • GEO/GSE44784
  • GEO/GSE44785