CNBP controls IL-12 gene transcription and Th1 immunity

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-B)–dependent proinflammatory cytokine gene expression. Here, we generated mice lacking CNBP and found that CNBP regulates a very restricted gene signature that includes IL-12β. 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-B/Rel signaling normally but were impaired in their ability to control the activation of c-Rel, a key driver of IL-12β 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-12β, as well as a reduced T helper type 1 (Th1) cell IFN- response essential to controlling parasite replication. Collectively, these findings identify CNBP as important regulator of c-Rel–dependent IL-12β gene transcription and Th1 immunity.

Source: The Journal of Experimental Medicine - December 3, 2018 Category: Internal Medicine Authors: Chen, Y., Sharma, S., Assis, P. A., Jiang, Z., Elling, R., Olive, A. J., Hang, S., Bernier, J., Huh, J. R., Sassetti, C. M., Knipe, D. M., Gazzinelli, R. T., Fitzgerald, K. A. Tags: Innate Immunity and Inflammation Articles Source Type: research