关键词: allergy dendritic cells intestine lactic acid bacteria regulatory T cells

Mesh : Animals T-Lymphocytes, Regulatory / immunology Dendritic Cells / immunology Mice Lymph Nodes / immunology Lactococcus lactis / immunology Cell Differentiation / immunology Mice, Inbred BALB C Mesentery / immunology Cytokines / metabolism Mice, Transgenic Lymphocyte Activation / immunology Coculture Techniques Female

来  源:   DOI:10.3389/fimmu.2024.1395380   PDF(Pubmed)

Abstract:
UNASSIGNED: 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 Lactococcus lactis subsp. cremoris 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 L. cremoris YRC3780 ameliorates the symptoms of pollinosis in both animal and human studies.
UNASSIGNED: CD11c+ cells from mesenteric lymph nodes (MLNs) of BALB/c mice were cultured as MLN DCs with L. cremoris 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 L. cremoris 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 L. cremoris YRC3780 were used to examine the recognition of YRC3780 by MLN DCs.
UNASSIGNED: L. cremoris YRC3780 enhanced the expression of genes involved in Treg induction in MLN DCs and induced Foxp3+CD4+T 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 L. cremoris 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.
UNASSIGNED: Our findings provide insights into the modulation of intestinal immune responses mediated by DCs and the antiallergic effects of lactic acid bacteria.
摘要:
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(DC)尤其重要。然而,肠道DCs对食物免疫反应的调节一直缺乏描述。在这项研究中,我们分析了乳酸乳球菌亚种的作用。cremorisYRC3780,一种从开菲尔分离的乳酸菌菌株,一种传统的发酵奶制品,关于肠道DC对T细胞的抗原呈递诱导的免疫应答以及这些免疫调节作用的作用机制。已经显示,在动物和人类研究中,L.cremorisYRC3780改善花粉症的症状。
将来自BALB/c小鼠的肠系膜淋巴结(MLN)的CD11c+细胞作为MLNDCs与CremorisL.YRC3780一起培养,并通过qPCR检查诱导调节性T细胞(Tregs)的基因表达。此外,MLNDC与来自DO11.10转基因小鼠的CD4+T细胞共培养,所述小鼠表达卵清蛋白(OVA)特异性TCR和OVA抗原肽和CremorisL.YRC3780。通过流式细胞术检查Tregs的诱导,通过DNA微阵列和qPCR分析基因表达,并通过ELISA测量细胞因子的产生。使用来自TLR2缺陷型小鼠的MLNDCs和CremorisL.YRC3780的组分来检查MLNDCs对YRC3780的识别。
L.cremorisYRC3780增强了MLNDC中Treg诱导基因的表达,并在MLNDC和CD4T细胞共培养系统中诱导了Foxp3CD4T细胞。对MLNDCs的作用可能是由TLR2以外的受体介导的。结合CD4+T细胞基因表达和细胞因子ELISA的微阵列分析,已经证明了乳脂乳杆菌YRC3780促进了Th1和Tregs的诱导,并通过MLNDCs的抗原呈递调节涉及多个基因的Th1/Th2和Treg/Th17细胞的平衡。
我们的发现为DC介导的肠道免疫应答的调节和乳酸菌的抗过敏作用提供了见解。
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