Functional maturation of intestinal immunoregulatory cells by food components

越来越多的证据表明，CD 4 ^+调节性T细胞（T_2<reg>）在维持外周免疫耐受中起着重要作用，可预防移植过程中引起的过敏、自身免疫性疾病和炎症等免疫紊乱，而粘膜表面，尤其是胃肠道结构（GI truct）是诱导机体对外源性抗原耐受的必经部位。因此，它似乎配备了微环境优选的诱导适应性和抗原特异性的调节性T细胞。细胞因子环境包括TGF-β和IL-10以旁分泌和自分泌的方式特别影响局部树突状细胞和诱导的调节性T细胞（iTreg）的效应子功能。使用这样的益生菌菌株之一，Lactococcus Lactis cremoris C60，我们已经表明，不仅细菌，而且它们的热水提取物（C60 Ex）通过MyD 88依赖性途径诱导树突状细胞产生高IL-10。细菌组分的效应分子被鉴定为多糖和核苷酸，其分别使用TLR 2和TLR 9作为产生IL-10的主要途径。经口给予BALB/c小鼠C60 Ex导致在其肠派伊尔集合淋巴结和肠系膜淋巴结中诱导产生IL-10和IFN-γ的T细胞，表明食物成分如益生菌是肠道iTreg功能成熟的重要因素。

There are accumulating evidence that CD4^+ regulatory T cells (T_<reg>) play a pivotal role in the maintenance of peripheral tolerance, thus preventing immune disorders such as allergy, autoimmune diseases and inflammation induced during transplantation.Mucosal surface, especially gastrointestinal truct (GI truct), is an obligatory site for tolerance induction against numerous exogenous antigens that it encounter. Therefore it seems to be equipped with microenvironment preferable for the induction of adaptive and antigen-specific regulatory T cells. Cytokine milieu including TGF-β and IL-10 particularly affects effector function of local dendritic cells and induced regulatory T cells (iTreg) in both paracrine and autocrine fashion.In the present study, we have screened probiotic strains (lactic acid bacteria) which induce high production of IL-10 from dendritic cells. Using one of such probiotic strains, Lactococcus Lactis cremoris C60, we have shown that not only bacteria but also hot water extract of them (C60Ex) induce high IL-10 production from dendritic cells via MyD88-dependent pathway. Effector molecules of bacteria components are identified as polysaccharides and nucleotides which use TLR2 and TLR9 as major pathways for IL-10 production, respectively.Oral administration of C60Ex to BALB/c mice resulted in the induction of IL-10 and IFN-gamma producing T cells in their intestinal Peyer's patches and mesenteric lymph nodes, indicating that food components such as probiotic bacteria are important factors for functional maturation of intestinal iTreg.