PPARδ-null mice with EAE also exhibited a severe inflammatory response in their spinal cord—they had a higher frequency of CD4+ cells that had an accumulation of IFN-γ or IL-17A compared to WT mice [20]. Intriguingly, PPARδ also appears to play a protective role in the spinal cords of steroid-receptor-coactivator-3-(SRC-3-) null mice with EAE. SRC-3-null mice had a significantly reduced severity of EAE that was associated with diminished inflammatory responses and decreased demyelination. The attenuated EAE symptoms in SRC-3-null mice are thought to occur via upregulation of PPARδ. SRC-3-null mice displayed decreased expression of the proinflammatory markers, TNF-α, IFN-γ, CCL2, CCL3, CCL5, and CXCL10, and increased expression of the anti-inflammatory markers, IL-10 and opsonins. Myelin genes—myelin basic protein (MBP) and PLP—were also significantly higher in SRC-3-null mice, which may be a result of increased PPARδ expression [51].
