%0 Journal Article
%T CNBP controls IL-12 gene transcription and Th1 immunity
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20181031
%X An inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. Recently, cellular nucleic acid每binding protein (CNBP) was identified as a regulator of nuclear factor-kappaB (NF-百B)每dependent proinflammatory cytokine gene expression. Here, we generated mice lacking CNBP and found that CNBP regulates a very restricted gene signature that includes IL-12汕. 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-百B/Rel signaling normally but were impaired in their ability to control the activation of c-Rel, a key driver of IL-12汕 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-12汕, as well as a reduced T helper type 1 (Th1) cell IFN-污 response essential to controlling parasite replication. Collectively, these findings identify CNBP as important regulator of c-Rel每dependent IL-12汕 gene transcription and Th1 immunity.
%U http://jem.rupress.org/content/215/12/3136