| First Author | Drohomyrecky PC | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 10 | Pages | 2588-2601 |
| PubMed ID | 31578267 | Mgi Jnum | J:282042 |
| Mgi Id | MGI:6370239 | Doi | 10.4049/jimmunol.1801200 |
| Citation | Drohomyrecky PC, et al. (2019) Peroxisome Proliferator-Activated Receptor-delta Acts within Peripheral Myeloid Cells to Limit Th Cell Priming during Experimental Autoimmune Encephalomyelitis. J Immunol 203(10):2588-2601 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR)-delta is a fatty acid-activated transcription factor that regulates metabolic homeostasis, cell growth, and differentiation. Previously, we reported that mice with a global deficiency of PPAR-delta develop an exacerbated course of experimental autoimmune encephalomyelitis (EAE), highlighting a role for this nuclear receptor in limiting the development of CNS inflammation. However, the cell-specific contribution of PPAR-delta to the more severe CNS inflammatory response remained unclear. In this study, we studied the specific involvement of PPAR-delta in myeloid cells during EAE using mice that had Cre-mediated excision of floxed Ppard driven by the lysozyme M (LysM) promoter (LysM (Cre) :Ppard (fl/fl)). We observed that LysM (Cre) :Ppard (fl/fl) mice were more susceptible to EAE and developed a more severe course of this disease compared with Ppard (fl/fl) controls. The more severe EAE in LysM (Cre) :Ppard (fl/fl) mice was associated with an increased accumulation of pathogenic CD4(+) T cells in the CNS and enhanced myelin-specific Th1 and Th17 responses in the periphery. Adoptive transfer EAE studies linked this EAE phenotype in LysM (Cre) :Ppard (fl/fl) mice to heightened Th responses. Furthermore, studies using an in vitro CD11b(+) cell:Th cell coculture system revealed that CD11b(+)CD11c(+) dendritic cells (DC) from LysM (Cre) :Ppard (fl/fl) mice had a heightened capacity to prime myelin oligodendrocyte glycoprotein (MOG)-specific Th cells compared with Ppard (fl/fl) counterparts; the effects of DC on Th1 cytokine production were mediated through production of the IL-12p40 homodimer. These studies revealed a role for PPAR-delta in DC in limiting Th cell priming during EAE. |
