Kiyono H, Kweon M N, Hiroi T, Takahashi I
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Acta Odontol Scand. 2001 Jun;59(3):145-53. doi: 10.1080/000163501750266738.
The mucosal immune system is a first line of defense against foreign antigens, including microbial and dietary antigens. Under normal circumstances, the mucosal immune system employs tightly regulated dynamic mucosal intra- and internets consisting of inductive and effector sites for the induction of an appropriate immunological homeostasis between the host and mucosal environments. The common mucosal immune system (CMIS), which interconnects between inductive (e.g. Peyer patch) and effector (e.g. intestinal lamina propria) tissues for the induction of the IgA response, is well characterized. Recent results provide strong evidence for the presence of a CMIS-independent IgA induction pathway. Two distinct subsets of mucosal IgA-committed B cells termed B-1 and B-2, are associated with CMIS-independence and CMIS-dependent cascades respectively. In some cases, the breakdown of this tightly regulated mucosal immune system leads to pathological responses to different gut environmental antigens. As a result, disorders such as inflammatory bowel disease (e.g. IBD) and allergic gastroenteropathy can be evoked in the gastrointestinal tissues. Recently, many studies have described possible molecular and cellular mechanisms for this dysfunction in the gastrointestinal tissues by using murine models with specific gene manipulation. In this review we summarize recent findings from our group concerning the CMIS-dependent and CMIS-independent IgA induction pathways and gastrointestinal diseases (IBD and intestinal allergic diseases). These observations may provide useful information for the development of new mucosal immune therapy.
黏膜免疫系统是抵御外来抗原（包括微生物和饮食抗原）的第一道防线。在正常情况下，黏膜免疫系统利用由诱导部位和效应部位组成的严格调控的动态黏膜内网络和网络间结构，以在宿主与黏膜环境之间诱导适当的免疫稳态。相互连接诱导组织（如派尔集合淋巴结）和效应组织（如肠固有层）以诱导IgA应答的共同黏膜免疫系统（CMIS）已得到充分表征。最近的研究结果为存在一条不依赖CMIS的IgA诱导途径提供了有力证据。黏膜IgA定向B细胞的两个不同亚群，分别称为B-1和B-2，它们分别与不依赖CMIS和依赖CMIS的级联反应相关。在某些情况下，这种严格调控的黏膜免疫系统的破坏会导致对不同肠道环境抗原的病理反应。结果，胃肠道组织中可能引发诸如炎症性肠病（如IBD）和过敏性胃肠病等疾病。最近，许多研究通过使用具有特定基因操作的小鼠模型，描述了胃肠道组织中这种功能障碍可能的分子和细胞机制。在这篇综述中，我们总结了我们小组关于依赖CMIS和不依赖CMIS的IgA诱导途径以及胃肠道疾病（IBD和肠道过敏性疾病）的最新发现。这些观察结果可能为开发新的黏膜免疫疗法提供有用信息。
