Sphingoid base in pineapple glucosylceramide suppresses experimental allergy by binding leukocyte mono‐immunoglobulin‐like receptor 3

BACKGROUND: The increase in patients suffering from type I hypersensitivity, including hay fever and food allergy, is a serious public health issue around the world. Recent studies have focused on allergy prevention by food factors with fewer side effects. The purpose of this study was to evaluate the effect of dietary glucosylceramide from pineapples (P‐GlcCer) on type I hypersensitivity and elucidate mechanisms. RESULTS: Oral administration of P‐GlcCer inhibited ear edema in passive cutaneous anaphylaxis reaction. In a Caco‐2/RBL‐2H3 co‐culture system, P‐GlcCer inhibited β‐hexosaminidase release from RBL‐2H3 cells. The direct treatment of P‐GlcCer on RBL‐2H3 did not affect β‐hexosaminidase release, but sphingoid base moiety of P‐GlcCer did. These results predicted that sphingoid base, a metabolite of P‐GlcCer, through the intestine inhibited type I hypersensitivity by inhibiting mast cell degranulation. In addition, the inhibitory effects of P‐GlcCer on ear edema and degranulation of RBL‐2H3 cells were canceled by pretreatment of leukocyte mono‐immunoglobulin‐like receptor 3 (LMIR3)‐Fc, which can block LMIR3‐mediated inhibitory signals. CONCLUSION: It was demonstrated that a sphingoid base, one of the metabolites of P‐GlcCer, may inhibit mast cell degranulation by binding to LMIR3. The oral administration of P‐GlcCer is a novel and attractive food factor that acts directly on mast cells to suppress allergy. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.