Sensing danger through a "finger"

Abstract

In this issue of JEM, the study by Chen et al. (https://doi.org/10.1084/jem.20181031) reveals a previously unrecognized role of cellular nucleic acid-binding protein (Cnbp) as a novel transcriptional regulator of interleukin-12β (IL-12β) transcription and IL-12-driven, Th1-mediated immune responses, which has important implications for both host defense and inflammatory disease.

Insights from Xiaojing Ma.

Cnbp regulates IL-12β gene transcription, IL-12 production, and Th1 immunity. Cnbp resides in the cytosol of macrophages and translocates to the nucleus in response to diverse microbial pathogens and pathogen-derived products through the TLR–MyD88–IRAK–TAK1 signaling pathway. Cnbp has a selective 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 require Cnbp. Furthermore, Cnbp itself binds the IL-12β promoter. Principally through its IL-12–augmenting activity in APCs, Cnbp enhances the Th1-mediated IFN-γ response to acute toxoplasmosis to control parasite replication.