MiR-146a and NF-κB1 Regulate Mast Cell Survival and T Lymphocyte Differentiation

Mol Cell Biol. 2012 Nov;32(21):4432-44. doi: 10.1128/MCB.00824-12. Epub 2012 Aug 27.

Abstract

The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell memory formation. Increased mast cell survival was due to unbalanced expression of pro- and antiapoptotic factors and particularly to the complete inability of p50-deleted mast cells to induce expression of miR-146a, which in the context of mast cell survival acted as a proapoptotic factor. Interestingly, in a different cellular context, namely, human and mouse primary T lymphocytes, miR-146a and NF-κB p50 did not influence cell survival or cytokine production but rather T cell expansion and activation in response to T cell receptor (TCR) engagement. Our data identify a new molecular network important in modulating adaptive and innate immune responses and show how the same activation-induced microRNA (miRNA) can be similarly regulated in different cell types even in response to different stimuli but can still determine very different outcomes, likely depending on the specific transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Immunologic Memory
  • Lymphocyte Activation / genetics
  • Mast Cells / immunology
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / biosynthesis
  • MicroRNAs / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit / deficiency*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, CCR7 / biosynthesis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*

Substances

  • CCR7 protein, human
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7