T-cells cross the blood–brain/spinal barrier and secrete various cytokines, including IFNγ (interferon γ), IL-17, and TNFα, all of which can damage myelin and neurons. These processes play an integral role during neurological insult. For example, MS is mediated primarily by autoreactive T-cells of the Th1 (T helper type 1) or Th17 phenotype (Trinchieri et al., 2003; Fletcher et al., 2010). Given that T-cells express PPARα and PPARγ, these PPARs can influence the adaptive immune system by modifying the activity of these cells (Marx et al., 2002). Several studies show that agonists for all three PPAR isoforms inhibit Th1-cell expansion and cytokine production, and in some cases, can concomitantly increase expression of Th2 cytokines (Niino et al., 2001; Diab et al., 2002, 2004; Feinstein et al., 2002; Gocke et al., 2009; Kanakasabai et al., 2010). This may explain why Th1 responses are enhanced in PPARγ-deficient mice, and EAE pathology is exacerbated in mice treated with PPARγ antagonists (Natarajan et al., 2003; Raikwar et al., 2005).
