CNBP controls c-Rel dependent IL-12β gene transcription and Th1 immunity

Summary An inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. Herein, we identified Cellular nucleic acid binding protein (Cnbp) as a specific regulator of interleukin-12β gene transcription and Th1 immunity. Cnbp resides in the cytosol of macrophages and translocates to the nucleus in response to a broad range of microbial ligands. Cnbp-deficient macrophages had a selective impairment in their ability to induce IL12β gene transcription. Cnbp interacted with c-Rel, an NFκB/Rel family member that controls IL12β gene transcription. c-Rel nuclear translocation and DNA binding activity were dependent on Cnbp. Furthermore, Cnbp itself bound the IL12β promoter. Lastly, Cnbp-deficient mice were more susceptible to acute toxoplasmosis associated with reduced production of IL12β, as well as a reduced Th1 cell IFNγ response essential to control parasite replication. Collectively, these findings identify Cnbp as a key regulator of c-Rel dependent IL12β gene transcription and Th1 immunity.