Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells

Figure 11

VPA polarizes Th1 and Th17 immune profiles into Th2 immune responses, both in vitro and in vivo. Th0, or naïve lymphocytes, that are activated in vitro with anti-CD3 and anti-CD28 and then polarized into Th1 with IL-2 or into Th17 with TGF-β+IL-6+TNF-α+IL-1β and which are then treated with VPA, are polarized toward a Th2 profile due to increased expression of GATA3 and IL-4. This reduces the expression levels of T-bet and IFN-γ (Th1), as well as of RORγt and IL-17 (Th17). This effect is also found in in vivo models of EAE, as well as in graft versus host disease. Additionally, VPA also induces apoptosis in Th1 and Th17, both in vitro and in vivo (not shown). Green arrows indicate the processes, molecules, or mediators in the signaling pathway that are augmented and/or promoted by VPA. Red arrows indicate processes, molecules, or mediators in the signaling pathway that are inhibited by VPA.