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Recently, we found a novel function of the lactic acid bacterium Tetragenococcus halophilus derived from miso, a fermented soy paste, that induces interleukin (IL)-22 production in B cells preferentially. IL-22 plays a critical role in barrier functions in the gut and skin. We further screened other bacteria species, namely, Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Weissella, Pediococcus, and Bacillus, in addition to Tetragenococcus and found that some of them possessed robust IL-22-inducible function in B cells in vitro. This process resulted in the augmented expression of activation markers CD86 and CD69 on B and T cells, respectively. However, these observations were not correlated with IL-22 production. We isolated Bacillus coagulans sc-09 from miso and determined it to be the best strain to induce robust IL-22 production in B cells. Furthermore, feeding B. coagulans sc-09 to mice augmented the barrier function of the skin regardless of gut microbiota.

Propolis possesses several immunological functions. We recently generated a conditional Ca2+ biosensor yellow cameleon (YC3.60) transgenic mouse line and established a five-dimensional (5D) (x, y, z, time, and Ca2+ signaling) system for intravital imaging of lymphoid tissues, including Peyer's patches (PPs). To assess the effects of propolis on immune cells, we analyzed Ca2+ signaling in vitro and in vivo using CD11c-Cre/YC3.60flox transgenic mice, in which CD11c+ dendritic cells (DCs) specifically express YC3.60. We found that propolis induced Ca2+ signaling in DCs in the PPs. Intravital imaging of PPs also showed that an intraperitoneal injection of propolis augmented Ca2+ signaling in CD11c+ cells, suggesting that propolis possesses immune-stimulating activity. Furthermore, CD11c+ cells in PPs in mice administrated propolis indicated an increase in Ca2+ signaling. Our results indicate that propolis induces immunogenicity under physiological conditions.