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_&lt；reg&gt；)在维持外周免疫耐受中起关键作用，从而预防移植过程中引起的免疫紊乱，如过敏、自身免疫性疾病和炎症。粘膜表面，特别是胃肠道结构，是诱导对其所遇到的众多外源性抗原的耐受的必备部位。因此，它似乎具有较好的诱导适应性和抗原特异性调节性T细胞的微环境。包括转化生长因子-β和IL-10在内的细胞因子环境特别影响局部树突状细胞的效应功能，并以旁分泌和自分泌的方式诱导调节性T细胞。利用其中一株益生菌乳杆菌C60，我们发现不仅细菌，而且其热水提取物(C60Ex)都通过MyD88依赖的途径诱导树突状细胞产生高水平的IL-10。BALB/c小鼠口服C60Ex后，肠道Peyer‘s结和肠系膜淋巴结中产生IL-10和干扰素-γ的T细胞均被诱导，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.