A model for PPARα-mediated protection in EAE. In the presence of PPARα agonists, PPARα heterodimerizes with RXR, dissociates from its nuclear corepressor complex, associates with a coactivator complex, and binds to PPREs in the promoter region of IL-4 and/or IL-5. The trans-activation of IL-4/IL-5 leads to increased expression of GATA3, which in turn results in decreased T-bet expression and down-regulation of the Th1/Th17 inflammatory response. This shift in the immune response to a Th2-like phenotype results in amelioration of EAE.