Takayama Naoko, Igarashi Osamu, Kweon Mi-Na, Kiyono Hiroshi
Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Clin Immunol. 2007 May;123(2):199-208. doi: 10.1016/j.clim.2007.01.007. Epub 2007 Mar 13.
Intestinal allergic diseases are initiated by aberrant Th2-type immune responses, including elevation of IgE antibodies (Abs) and infiltration of eosinophils. However, little is known about the role of Peyer's patches (PP) in the control of allergic diseases. Using a mouse model for food allergy, we here show that mice lacking PP are more susceptible to disease development and show higher levels of antigen-specific IgE Abs than do PP-intact mice. In our study, we noted that high numbers of eosinophils infiltrated into the small intestine of PP-null mice. In contrast, the PP of intact mice contained regulatory CD4+CD25+ Foxp3+ T cells (Treg) that are known to produce high levels of IL-10, and inhibited the development of allergic diarrhea. PP-intact mice thus developed allergic diarrhea when treated with anti-CD25 or anti-IL-10 monoclonal antibody (mAb) in vivo. These studies demonstrate that PP, as the site where IL-10-producing Treg cells are created, mediate the mucosal regulatory network for the control of undesired allergic responses in the intestine.
肠道过敏性疾病由异常的Th2型免疫反应引发，包括IgE抗体升高和嗜酸性粒细胞浸润。然而，关于派尔集合淋巴结（PP）在控制过敏性疾病中的作用知之甚少。利用食物过敏小鼠模型，我们在此表明，缺乏PP的小鼠更易患疾病，且与PP完整的小鼠相比，其抗原特异性IgE抗体水平更高。在我们的研究中，我们注意到大量嗜酸性粒细胞浸润到PP缺失小鼠的小肠中。相比之下，完整小鼠的PP含有已知能产生高水平IL-10的调节性CD4+CD25+ Foxp3+ T细胞（Treg），并抑制过敏性腹泻的发展。因此，在体内用抗CD25或抗IL-10单克隆抗体（mAb）处理时，PP完整的小鼠会发生过敏性腹泻。这些研究表明，作为产生IL-10的Treg细胞生成部位的PP，介导了肠道中控制不良过敏反应的黏膜调节网络。
