LAUSR

HIGHLIGHTSCebpb−/− mice are resistant to EAE.In vivo Th17 responses are impaired in absence of C/EBP&bgr;.Th17 differentiation is normal in APC‐free cultures.C/EBP&bgr; binds to the IL‐23R in myeloid and Th17 cells. ABSTRACT The CCAAT/Enhancer Binding Protein &bgr; (C/EBP&bgr;) transcription factor is activated by multiple inflammatory stimuli, including IL‐17 and LPS, and C/EBP&bgr; itself regulates numerous genes involved in inflammation. However, the role of C/EBP&bgr; 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/EBP&bgr; in myeloid lineage cell activation as the likely mechanism for defective Th17 priming in vivo. However, we did uncover an unexpected role for C/EBP&bgr; in regulating ll23r expression in APCs. ChIP assays confirmed that C/EBP&bgr; binds directly to the Il23r gene promoter in dendritic cells and Th17 cells. These data establish C/EBP&bgr; as a key driver of autoimmune inflammation in EAE, and propose a novel role for C/EBP&bgr; in regulation of IL‐23R expression.