miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

J Exp Med. 2011 Jun 6;208(6):1189-201. doi: 10.1084/jem.20101823. Epub 2011 May 9.

Abstract

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Autoimmunity*
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Female
  • Humans
  • Inflammation
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Lipopolysaccharides / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • RNA Processing, Post-Transcriptional
  • TNF Receptor-Associated Factor 6 / metabolism
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Lipopolysaccharides
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • TNF Receptor-Associated Factor 6
  • Interleukin-1 Receptor-Associated Kinases
  • Irak1 protein, mouse