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Publication : MiR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation.

First Author  Rusca N Year  2012
Journal  Mol Cell Biol Volume  32
Issue  21 Pages  4432-44
PubMed ID  22927641 Mgi Jnum  J:189248
Mgi Id  MGI:5444797 Doi  10.1128/MCB.00824-12
Citation  Rusca N, et al. (2012) miR-146a and NF-kappaB1 Regulate Mast Cell Survival and T Lymphocyte Differentiation. Mol Cell Biol 32(21):4432-44
abstractText  The transcription factor NF-kappaB 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-kappaB family member NF-kappaB1 (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-kappaB 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.
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