miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

Nicole Rusca, Lorenzo Dehò, Sara Montagner, Christina E. Zielinski, Antonio Sica, Federica Sallusto, Silvia Monticelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4432-4444
Number of pages13
JournalMolecular and Cellular Biology
Volume32
Issue number21
DOIs
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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