| First Author | Chen Y | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 12 | Pages | 3136-3150 |
| PubMed ID | 30442645 | Mgi Jnum | J:267851 |
| Mgi Id | MGI:6268943 | Doi | 10.1084/jem.20181031 |
| Citation | Chen Y, et al. (2018) CNBP controls IL-12 gene transcription and Th1 immunity. J Exp Med 215(12):3136-3150 |
| abstractText | An inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. Recently, cellular nucleic acid-binding protein (CNBP) was identified as a regulator of nuclear factor-kappaB (NF-kappaB)-dependent proinflammatory cytokine gene expression. Here, we generated mice lacking CNBP and found that CNBP regulates a very restricted gene signature that includes IL-12beta. CNBP resides in the cytosol of macrophages and translocates to the nucleus in response to diverse microbial pathogens and pathogen-derived products. Cnbp-deficient macrophages induced canonical NF-kappaB/Rel signaling normally but were impaired in their ability to control the activation of c-Rel, a key driver of IL-12beta gene transcription. The nuclear translocation and DNA-binding activity of c-Rel required CNBP. Lastly, Cnbp-deficient mice were more susceptible to acute toxoplasmosis associated with reduced production of IL-12beta, as well as a reduced T helper type 1 (Th1) cell IFN-gamma response essential to controlling parasite replication. Collectively, these findings identify CNBP as important regulator of c-Rel-dependent IL-12beta gene transcription and Th1 immunity. |
