Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
R&D Center, Yotsuba Milk Products, Co., Ltd., Kitahiroshima, Japan.
Front Immunol. 2024 Jul 8;15:1395380. doi: 10.3389/fimmu.2024.1395380. eCollection 2024.
The intestinal immune system plays a pivotal role in the induction of immune responses against food. In the case of T cell response, dendritic cells (DCs) are especially important. However, the regulation of immune responses to food by intestinal DCs has been poorly described. In this study, we analyzed the effect of subsp. YRC3780, a lactic acid bacterial strain isolated from kefir, a traditional fermented milk product, on the immune responses induced by antigen presentation by intestinal DCs to T cells as well as the mechanism of action of these immunomodulatory effects. It has been shown that YRC3780 ameliorates the symptoms of pollinosis in both animal and human studies.
CD11c cells from mesenteric lymph nodes (MLNs) of BALB/c mice were cultured as MLN DCs with YRC3780 and expression of genes inducing regulatory T cells (Tregs) was examined by qPCR. In addition, MLN DCs were cocultured with CD4 T cells from DO11.10 transgenic mice expressing an ovalbumin (OVA)-specific TCR and the OVA antigen peptide and YRC3780. Induction of Tregs was examined by flow cytometry, gene expression was analyzed by DNA microarray and qPCR, and the production of cytokines was measured by ELISA. MLN DCs from TLR2-deficient mice and components of YRC3780 were used to examine the recognition of YRC3780 by MLN DCs.
YRC3780 enhanced the expression of genes involved in Treg induction in MLN DCs and induced Foxp3CD4T cells in an MLN DC and CD4 T-cell co-culture system. The effect on MLN DCs was likely mediated by receptors other than TLR2. Together with microarray analyses of CD4 T cell gene expression and cytokine ELISA, it was demonstrated that YRC3780 promoted the induction of Th1 and Tregs, and regulated the balance of Th1/Th2 and Treg/Th17 cells involving multiple genes via the antigen-presentation of MLN DCs.
Our findings provide insights into the modulation of intestinal immune responses mediated by DCs and the antiallergic effects of lactic acid bacteria.
肠道免疫系统在诱导针对食物的免疫反应中起着关键作用。在 T 细胞反应的情况下，树突状细胞（DCs）尤为重要。然而，肠道 DC 对食物免疫反应的调节作用还描述得很差。在这项研究中，我们分析了从开菲尔（一种传统发酵乳制品）中分离出的乳酸菌菌株 subsp. YRC3780 通过肠道 DC 对抗原呈递给 T 细胞诱导的免疫反应的影响，以及这些免疫调节作用的作用机制。已经表明，YRC3780 在动物和人类研究中都能改善花粉过敏的症状。
用 YRC3780 培养来自 BALB/c 小鼠肠系膜淋巴结（MLNs）的 CD11c 细胞，并用 qPCR 检测诱导调节性 T 细胞（Tregs）的基因表达。此外，将 MLN DC 与表达卵清蛋白（OVA）特异性 TCR 和 OVA 抗原肽的 DO11.10 转基因小鼠的 CD4 T 细胞共培养，并使用流式细胞术检测 Tregs 的诱导，用 DNA 微阵列和 qPCR 分析基因表达，用 ELISA 测量细胞因子的产生。使用 TLR2 缺陷型小鼠的 MLN DC 和 YRC3780 的成分来检查 MLN DC 对 YRC3780 的识别。
YRC3780 增强了 MLN DC 中参与 Treg 诱导的基因表达，并在 MLN DC 和 CD4 T 细胞共培养系统中诱导 Foxp3CD4T 细胞。这种对 MLN DC 的影响可能是由 TLR2 以外的受体介导的。结合对 CD4 T 细胞基因表达的微阵列分析和细胞因子 ELISA，证明 YRC3780 通过 MLN DC 的抗原呈递促进 Th1 和 Tregs 的诱导，并调节 Th1/Th2 和 Treg/Th17 细胞的平衡，涉及多个基因。
我们的研究结果提供了对 DC 介导的肠道免疫反应调节和乳酸菌抗过敏作用的深入了解。
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