CCAAT/Enhancer-binding protein β promotes pathogenesis of EAE. (April 2017)

• Record Type: Journal Article
• Authors: Simpson-Abelson, Michelle R.; Hernandez-Mir, Gerard; Childs, Erin E.; Cruz, J. Agustin; Poholek, Amanda C.; Chattopadhyay, Ansuman; Gaffen, Sarah L.; McGeachy, Mandy J.
• Is Part Of: Cytokine. Volume 92(2017)
• Page Start: 24
• Page End: 32
• Publication Date: 2017-04
• Subjects: C/EBPβ -- Transcription factor -- EAE -- IL-17 -- Th17 -- IL-23R; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2017.01.005
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Cebpb −/− mice are resistant to EAE. In vivo Th17 responses are impaired in absence of C/EBPβ. Th17 differentiation is normal in APC-free cultures. C/EBPβ binds to the IL-23R in myeloid and Th17 cells. 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.