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Cytokine. 2017 Apr;92:24-32. doi: 10.1016/j.cyto.2017.01.005. Epub 2017 Jan 12.

CCAAT/Enhancer-binding protein β promotes pathogenesis of EAE.

Author information

1
Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
2
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, Children's Hospital of UPMC, Pittsburgh, PA, USA.
3
Molecular Biology Information Service, Health Sciences Library System, University of Pittsburgh, Pittsburgh, PA, USA.
4
Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: Sarah.Gaffen@pitt.edu.
5
Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: Mmcgeach@pitt.edu.

Abstract

The CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor is activated by multiple inflammatory stimuli, including IL-17 and LPS, and C/EBPβ itself regulates numerous genes involved in inflammation. However, the role of C/EBPβ in driving autoimmunity is not well understood. Here, we demonstrate that Cebpb-/- mice are resistant to EAE. Cebpb-/- mice exhibited reduced lymphocyte and APC infiltration into CNS following EAE induction. Furthermore, MOG-induced Th17 cytokine production was impaired in draining LN, indicating defects in Th17 cell priming. In vitro Th17 polarization studies indicated that T cell responses are not inherently defective, instead supporting the known roles for C/EBPβ in myeloid lineage cell activation as the likely mechanism for defective Th17 priming in vivo. However, we did uncover an unexpected role for C/EBPβ in regulating ll23r expression in APCs. ChIP assays confirmed that C/EBPβ binds directly to the Il23r gene promoter in dendritic cells and Th17 cells. These data establish C/EBPβ as a key driver of autoimmune inflammation in EAE, and propose a novel role for C/EBPβ in regulation of IL-23R expression.

KEYWORDS:

C/EBPβ; EAE; IL-17; IL-23R; Th17; Transcription factor

PMID:
28088614
PMCID:
PMC5337143
DOI:
10.1016/j.cyto.2017.01.005
[Indexed for MEDLINE]
Free PMC Article

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