Author | Chen, Yongzhi | |
Author | Sharma, Shruti | |
Author | Assis, Patricia A. | |
Author | Jiang, Zhaozhao | |
Author | Elling, Roland | |
Author | Olive, Andrew J. | |
Author | Hang, Saiyu | |
Author | Bernier, Jennifer | |
Author | Huh, Jun R. | |
Author | Sassetti, Christopher M. | |
Author | Knipe, David M. | |
Author | Gazzinelli, Ricardo Tostes | |
Author | Fitzgerald, Katherine A. | |
Access date | 2022-08-18T14:04:57Z | |
Available date | 2022-08-18T14:04:57Z | |
Document date | 2018 | |
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. | pt_BR |
ISSN | 0022-1007 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/54708 | |
Sponsorship | NATIONAL INSTITUTES OF HEALTH | pt_BR |
Language | eng | pt_BR |
Publisher | Rockefeller University Press | pt_BR |
Rights | open access | pt_BR |
Title | CNBP controls IL-12 gene transcription and Th1 immunity | pt_BR |
Type | Article | pt_BR |
DOI | 10.1084/jem.20181031 | |
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. | pt_BR |
Affilliation | Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Department of Microbiology and Physiological Systems. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Division of Immunology. Department of Microbiology and Immunology. Harvard Medical School, Boston, MA, USA | pt_BR |
Affilliation | Program in Innate Immunity, Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Division of Immunology. Department of Microbiology and Immunology. Harvard Medical School. Boston, MA, USA | pt_BR |
Affilliation | Department of Microbiology and Physiological Systems. University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
Affilliation | Department of Microbiology and Immunology. Harvard Medical School. Boston, MA, USA | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | 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 | pt_BR |