Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 Induce the Expression of the REG3 Family in the Small Intestine of Mice via the Stimulation of Dendritic Cells and Type 3 Innate Lymphoid Cells

德氏乳杆菌保加利亚亚种 2038 和嗜热链球菌 1131 通过刺激树突状细胞和 3 型先天淋巴细胞诱导小鼠小肠中 REG3 家族的表达

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作者:Kyosuke Kobayashi, Yoshiko Honme, Toshihiro Sashihara

Abstract

Accumulating evidence clarifies that intestinal barrier function, for example, by the mucus layer, antimicrobial peptides, immune systems, and epithelial tight junctions, plays crucial roles in maintaining our health. We reported previously that yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 induced the gene expression of the regenerating family member 3 (REG3) family, which encodes antimicrobial peptides in the small intestine, although it was unclear how the yogurt activated the intestinal cells related to it. Here, we evaluated the cytokine production from the intestinal immune cells stimulated by these strains in vitro and in vivo to elucidate the mechanism for the induction of the REG3 family by the yogurt. The results showed that stimulation by both strains induced interleukin (IL)-23 production from bone marrow-derived dendritic cells (DCs) and IL-22 production from small intestinal lamina propria (LP) cells. In addition, oral administration of these strains to mice increased IL-23p19+ LPDCs and IL-22+ type 3 innate lymphoid cells and induced the expression of Reg3g in small intestinal tissue. Moreover, we showed that the activities for the induction of IL-23 by DCs were strain dependent on L. bulgaricus and S. thermophilus and that S. thermophilus 1131, which is the predominant species in the yogurt, exhibited relatively higher activity compared to the other strains of S. thermophilus. Our findings suggested that these yogurt starter strains, L. bulgaricus 2038 and S. thermophilus 1131, have the potential to maintain and improve intestinal barrier function by stimulating immune cells in the LP.

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