Bowman birk protease inhibitor suppresses GM-CSF, Th17 cells and CNS autoimmune inflammatory demyelination

Abstract Serine proteases play numerous roles in immune system and their inhibition modulates immune and autoimmune responses. Bowman Birk inhibitor (BBI), a soybean-derived serine protease inhibitor potently suppresses experimental autoimmune encephalitis (EAE) after oral administration. In this study, we show that BBI inhibits development of Th17 cells and reduces Th17 cell encephalitogenicity by suppressing their GM-CSF production and decreasing their numbers in the CNS of EAE mice. We also demonstrate that BBI induces IFN-γ production in Th17 cell culture, and that lack of IFN-γ or IFN-γR abrogates Th17 suppressive effect of BBI. In addition, BBI requires IL-27R, Stat-1, T-bet, and IL-10 to inhibit Th17 development. Taken together, our data demonstrate that BBI suppresses pathogenic Th17 cells through IFN- γ dependent pathway and ameliorates EAE. This suggests a novel immunomodulatory effect for serine protease inhibitors in immunity. In addition, BBI has potential to be safe oral therapy for autoimmune diseases, such as multiple sclerosis.