Tsuji Noriko M
Age Dimension Research Center, National Institute for Advanced Industrial Science and Technology (AIST), Japan.
Inflamm Allergy Drug Targets. 2006 Sep;5(3):191-201. doi: 10.2174/187152806778256043.
Mucosal surfaces, especially the gastrointestinal (GI) tract, are obligatory sites for tolerance induction against numerous exogenous antigens. Therefore, the mucosal surface seems to provide a microenvironment conductive to the induction of antigen-specific regulatory T cells. The cytokine milieu, which includes IL-10 and TGF-beta, affects effector function of local dendritic cells and induces regulatory T cells (iT(REG)). During immune homeostasis (steady state) in the GI tract, noninflammatory innate immune signals provided by innocuous or commensal bacteria seem to play important roles in the induction of regulatory cytokines that enable the establishment of tolerance, which involves iT(REG) function. In accordance with this viewpoint, utilizing physiological means such as probiotics and TLR ligands may improve the homeostatic conditions of immune-mediated diseases and inflammation. Antigen-specific iT(REG) is a great counterpart of thymus-derived CD25(+)CD4(+)Foxp3(+) T(REG) (nT(REG)), and therefore clinical applications of T(REG) should be developed that integrate the advantages of both of these cell populations. Close investigation of mucosal iT(REG) and related microenvironments not only will facilitate novel interventions of mucosal immunity but also will help to best utilize iT(REG) and iT(REG) in an integrated way.
黏膜表面，尤其是胃肠道，是诱导针对多种外源性抗原产生耐受性的必经部位。因此，黏膜表面似乎提供了一个有利于诱导抗原特异性调节性T细胞的微环境。包括白细胞介素-10和转化生长因子-β在内的细胞因子环境，会影响局部树突状细胞的效应功能并诱导调节性T细胞（诱导性调节性T细胞）。在胃肠道的免疫稳态（稳态）期间，无害或共生细菌提供的非炎性固有免疫信号，似乎在诱导能够建立耐受性的调节性细胞因子（这涉及诱导性调节性T细胞功能）方面发挥重要作用。根据这一观点，利用益生菌和Toll样受体配体等生理手段，可能会改善免疫介导疾病和炎症的稳态状况。抗原特异性诱导性调节性T细胞是胸腺来源的CD25(+)CD4(+)Foxp3(+)调节性T细胞（天然调节性T细胞）的理想对应物，因此应开发整合这两种细胞群体优势的调节性T细胞临床应用。对黏膜诱导性调节性T细胞及相关微环境的深入研究，不仅将促进黏膜免疫的新型干预措施，还将有助于以综合方式最佳利用诱导性调节性T细胞和天然调节性T细胞。
