Functional maturation of intestinal immunoregulatory cells by food components

越来越多的证据表明CD4^调节性T细胞（T_<reg>）在维持外周耐受中发挥着关键作用，从而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疾病。粘膜表面，特别是胃肠道（GI truct），是针对其遇到的多种外源抗原诱导耐受的必需部位。因此，它似乎具备有利于诱导适应性和抗原特异性调节性 T 细胞的微环境。包括 TGF-β 和 IL-10 在内的细胞因子环境特别以旁分泌和自分泌方式影响局部树突状细胞和诱导性调节性 T 细胞 (iTreg) 的效应功能。在本研究中，我们筛选了可诱导树突状细胞大量产生 IL-10 的益生菌菌株（乳酸菌）。使用此类益生菌菌株之一——乳脂乳球菌 C60，我们发现不仅是细菌，而且它们的热水提取物 (C60Ex) 通过 MyD88 依赖性途径诱导树突状细胞产生大量 IL-10。细菌成分的效应分子被确定为多糖和核苷酸，分别使用 TLR2 和 TLR9 作为产生 IL-10 的主要途径。 BALB/c 小鼠口服 C60Ex 后，在其肠道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，表明益生菌等食物成分是肠道 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.