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. |