Fermented plant product (FPP) suppresses immediate hypersensitivity reactions with impaired high-affinity IgE receptor (FcεRI) signaling

Fermented plant product (FPP) is a dietary supplement made by fermentation and aging of a variety of plants, including fruits, vegetables, and grains. A previous study has shown that oral FPP supplementation prevents the development of allergic rhinitis-like nasal symptoms in a murine model of Japanese cedar pollinosis without affecting systemic immune response. However, the mode of action by which FPP exerts an anti-allergic effect remains to be elucidated. Here, we show that FPP acts on mast cells to suppress immediate hypersensitivity reactions in vitro as well as in vivo. We found that stimulation with FPP potently suppressed IgE antibody-mediated degranulation of RBL-2H3 rat basophilic leukemia cells. We also found that oral feeding with FPP significantly suppressed passive cutaneous anaphylaxis (PCA), an in vivo model of IgE- and mast cell-mediated hypersensitivity reactions. Mechanistic analysis revealed that FPP extensively suppressed the high-affinity IgE receptor (Fc epsilon RI) signaling pathway, in which FPP not only inhibited intracellular Ca2+ influx upon Fc epsilon RI ligation but also negatively regulated another Ca2+-independent Fc epsilon RI signaling pathway leading to granule translocation through microtubule formation. These results suggest that FPP fulfills its anti-allergic activity by acting on the IgE-mast cell axis to suppress immediate hypersensitivity reactions.