| First Author | Tsai VW | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 48 | Pages | 17612-21 |
| PubMed ID | 22131422 | Mgi Jnum | J:178141 |
| Mgi Id | MGI:5297611 | Doi | 10.1523/JNEUROSCI.3449-11.2011 |
| Citation | Tsai VW, et al. (2011) CCAAT/Enhancer Binding Protein-delta Expression by Dendritic Cells Regulates CNS Autoimmune Inflammatory Disease. J Neurosci 31(48):17612-21 |
| abstractText | CCAAT enhancer binding protein-delta (C/EBPdelta) is a transcription factor that regulates inflammatory processes mediating bystander neuronal injury and CNS autoimmune inflammatory disease. The mechanism of the involvement of C/EBPdelta in these processes remains to be determined. Here, we examined the cellular source(s) and mechanisms by which C/EBPdelta may be involved in an animal model of multiple sclerosis. Mice deficient in C/EBPdelta expression exhibited less severe clinical disease than wild-type littermates in response to induction of experimental autoimmune encephalomyelitis (EAE) by vaccination with a myelin oligodendrocyte glycoprotein (MOG) fragment. This reduction in EAE severity was associated with a significant alteration in the complement of major CNS T-helper (Th) cell subtypes throughout disease, manifest as reduced ratios of Th17 cells to regulatory T-cells (Tregs). Studies in bone marrow chimeric mice indicated that C/EBPdelta expression by peripherally derived immune cells mediates C/EBPdelta involvement in EAE. Follow up in vitro and in vivo examination of dendritic cell (DC) mediated Th-cell development suggests that C/EBPdelta suppresses DC expression of interleukin-10 (IL-10), favoring Th17 over Treg development. In vitro and in vivo blockade of IL-10 signaling attenuated the effect of reduced C/EBPdelta expression by DCs on Th17:Treg ratios. These findings identify C/EBPdelta as an important DC transcription factor in CNS autoimmune inflammatory disease by virtue of its capacity to alter the Th17:Treg balance in an IL-10 dependent fashion. |
