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

The CCAAT/Enhancer Binding Protein ß (C/EBPß) transcription factor is activated by multiple inflammatory stimuli, including IL-17 and LPS, and C/EBPß itself regulates numerous genes involved in inflammation. However, the role of C/EBPß 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/EBPß in myeloid lineage cell activation as the likely mechanism for defective Th17 priming in vivo. However, we did uncover an unexpected role for C/EBPß in regulating ll23r expression in APCs. ChIP assays confirmed that C/EBPß binds directly to the Il23r gene promoter in dendritic cells and Th17 cells. These data establish C/EBPß as a key driver of autoimmune inflammation in EAE, and propose a novel role for C/EBPß in regulation of IL-23R expression.