| First Author | Simpson-Abelson MR | Year | 2017 |
| Journal | Cytokine | Volume | 92 |
| Pages | 24-32 | PubMed ID | 28088614 |
| Mgi Jnum | J:325834 | Mgi Id | MGI:6873661 |
| Doi | 10.1016/j.cyto.2017.01.005 | Citation | Simpson-Abelson MR, et al. (2017) CCAAT/Enhancer-binding protein beta promotes pathogenesis of EAE. Cytokine 92:24-32 |
| abstractText | The CCAAT/Enhancer Binding Protein beta (C/EBPbeta) transcription factor is activated by multiple inflammatory stimuli, including IL-17 and LPS, and C/EBPbeta itself regulates numerous genes involved in inflammation. However, the role of C/EBPbeta 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/EBPbeta in myeloid lineage cell activation as the likely mechanism for defective Th17 priming in vivo. However, we did uncover an unexpected role for C/EBPbeta in regulating ll23r expression in APCs. ChIP assays confirmed that C/EBPbeta binds directly to the Il23r gene promoter in dendritic cells and Th17 cells. These data establish C/EBPbeta as a key driver of autoimmune inflammation in EAE, and propose a novel role for C/EBPbeta in regulation of IL-23R expression. |
