Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/54708

Type
Article
Copyright
Open access
Collections
Share

Statistics
Metadata
Show full item record

CNBP CONTROLS IL-12 GENE TRANSCRIPTION AND TH1 IMMUNITY
Chen, Yongzhi et al. | Date Issued: 2018
Author
Chen, Yongzhi
Sharma, Shruti
Assis, Patricia A.
Jiang, Zhaozhao
Elling, Roland
Olive, Andrew J.
Hang, Saiyu
Bernier, Jennifer
Huh, Jun R.
Sassetti, Christopher M.
Knipe, David M.
Gazzinelli, Ricardo Tostes
Fitzgerald, Katherine A.
Affilliation
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA/Department of Immunology. Tufts University School of Medicine. Boston, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA
Department of Microbiology and Physiological Systems. University of Massachusetts Medical School. Worcester, MA, USA
Division of Immunology. Department of Microbiology and Immunology. Harvard Medical School, Boston, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA
Division of Immunology. Department of Microbiology and Immunology. Harvard Medical School. Boston, MA, USA
Department of Microbiology and Physiological Systems. University of Massachusetts Medical School. Worcester, MA, USA
Department of Microbiology and Immunology. Harvard Medical School. Boston, MA, USA
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA/Centre for Molecular Inflammation Research. Department of Cancer Research and Molecular Medicine. Trondheim, Norway
Abstract
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-kappa 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-12 beta. 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-kappa B/Ret signaling normally but were impaired in their ability to control the activation of c-Rel, a key driver of IL-12 beta 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 beta, as well as a reduced T helper type 1 (Th1) cell IFN-y response essential to controlling parasite replication. Collectively, these findings identify CNBP as important regulator of c-Ret-dependent IL-12 beta gene transcription and Th1 immunity.
Publisher
Rockefeller University Press
Citation
CHEN, Yongzhi et al. CNBP controls IL-12 gene transcription and Th1 immunity. J Exp Med., v. 215, n. 12, p. 3136-3150, 2018. doi: 10.1084/jem.20181031.
DOI
10.1084/jem.20181031
ISSN
0022-1007