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

Chen, Y.; Sharma, S.; Assis, P. A.; Jiang, Z.; Olive, A. J.; Hang, S.; Bernier, J.; Huh, J. R.; Sassetti, C. M.; Knipe, D. M.; Gazzinelli, R. T.; Fitzgerald, K. A.

doi:10.1101/258731

bioRxiv · 10.1101/258731

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

Chen, Y.·Sharma, S.·Assis, P. A.·Jiang, Z.·Olive, A. J.·Hang, S.·Bernier, J.·Huh, J. R.·Sassetti, C. M.·Knipe, D. M.·Gazzinelli, R. T.·Fitzgerald, K. A.

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Abstract

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-12{beta} 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 IL12{beta} gene transcription. Cnbp interacted with c-Rel, an NF{kappa}B/Rel family member that controls IL12{beta} gene transcription. c-Rel nuclear translocation and DNA binding activity were dependent on Cnbp. Furthermore, Cnbp itself bound the IL12{beta} promoter. Lastly, Cnbp-deficient mice were more susceptible to acute toxoplasmosis associated with reduced production of IL12{beta}, as well as a reduced Th1 cell IFN{gamma} response essential to control parasite replication. Collectively, these findings identify Cnbp as a key regulator of c-Rel dependent IL12{beta} gene transcription and Th1 immunity.

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Chen, Y., Sharma, S., Assis, P. A., Jiang, Z., Olive, A. J., Hang, S., Bernier, J., Huh, J. R., Sassetti, C. M., Knipe, D. M., Gazzinelli, R. T., Fitzgerald, K. A.. 2018-02-01. CNBP controls c-Rel dependent IL-12 β gene transcription and Th1 immunity. https://doi.org/10.1101/258731

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