Molecular mechanisms of oral immunity : Role of IL-5 in potentiation of IgA production in mucosal lymphoid cell

口腔免疫的分子机制：IL-5 在增强粘膜淋巴细胞 IgA 产生中的作用

基本信息

批准号：
10557036
负责人：
TAKATSU Kiyoshi
金额：
$ 7.36万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557036/
关键词：
IL-5 IL-6 IgA B-1 cell lamina propria Peyer's patch gene knock-out mouse IL-5 receptor クラス交換 **型T細胞リボ多糖体 γδ型T細胞

项目摘要

Interleukin-5 (IL-5) is Produced mainly by activated T lymphocytes and mast cells. It was originally recognized by its activity as a B cell growth factor and an IgA-enhancing factor. The IL-5 receptor (IL-5R) consists of two distinct membrane proteins, α and β chains. The binding of IL-5 occurs through the IL-5Rα, and the β chain forms a high affinity with IL-5Rα for the intracellular signal transduction pathway. IL-5, which has been shown to be an important cytokine for the mucosal immune system, possesses several immunological features which distinguish it from the systemic immune compartment. For example, IgA inductive tissues such as gut-associated lymphoreticular tissue (GALT) or Peyer's patches (PP) containing a high frequency of IgA-committed B cells [surface IgAィイD1+ィエD1 (sIgAィイD1+ィエD1) B cells and Th1/Th2 cells are interconnected with IgA effector sites including intestinal lamina propria (i-LP) via the common mucosal immune system (CMIS). IL-5 is a major cytokine which induce … More s sIgAィイD1+ィエD1 B cells to differentiate into IgA-producing plasma cells using mainly an in vitro system using PP and mitogen-stimulated splenic B cells. Further IL-2 and IL-6 have been demonstrated to be capable of enhancing IgA synthesis in vitro. An intriguing observation is that up to 40% of IgA-producing cells in the murine intestinal lamina propria arise from a pool of B-1 precursors derived from the peritoneal cavity. Peritoneal and lamina propria B-1 cells in mice have been shown to develop from a common pool and may represent a lineage separate from that of conventional PP B cells. These results suggest that B - 1 cells could be an important source for IgA-producing cells in mucosal tissues. We focused our study on exploring the role of IL-5R and B-1 cells in the development of IgA-producing cells in mucosa-associated tissues using the latter gene-disrupted murine model together with the background wild type mice.Deletion of IL-5Rα selectively influenced the mucosal IgA responses in vivo. While levels of IgA in mucosal secretions were more rduced in IL-5RαィイD1-/-ィエD1 mice than in wild type mice, the levels of IgA in serum were not changed. The frequency of IgA-producing cells was reduced in mucosal effector sites (e.g. intestinal lamina propria and nasal passage) but not in inductive sites such as PP and nasal-associated lymphoreticular, tissues (NALT) in IL-5RαィイD1-/-ィエD1 mice IgA-committed (surface IgAィイD1+ィエD1 ; sIgAィイD1+ィエD1) B-1 cells mainly resided in mucosal effector tissues, while conventional sIgAィイD1+ィエD1 B (B-2) cells formed in mucosal inductive sites of wild type mice. In contrast, in the effector tissue of IL-5RαィイD1-/-ィエD1 mice, sIgAィイD1+ィエD1 B-1 cells, but not sIgAィイD1+ィエD1 B-2 cells in the inductive site, were significantly reduced. IL-5Rα was more expressed on sIgAィイD1+ィエD1 B-1 cells than was IL-6R, while both IL-5Rα and IL-6R were expressed on sIgAィイD1+ィエD1 B-2 cells in wild type mice. sIgAィイD1+ィエD1 B-1 cells produced high levels of IgA with recombinant IL-5 (IL-5) rather than of IL-6 in vitro. Taken together, the findings demonstrate that the IL-5/IL-5R signaling pathway is critically important for the common mucosal immune system (CMIS) independent sIgAィイD1+ィエD1 B-1 cell development and for IgA responses in mucosal effector tissues in vivo. Less

白介素5（IL-5）主要由活化的T淋巴细胞和肥大细胞产生。它最初以其活性为B细胞生长因子和IgA增强因子而被认可。 IL-5受体（IL-5R）由两个不同的膜蛋白α和β链组成。 IL-5的结合通过IL-5Rα发生，β链与IL-5Rα对细胞内信号转导途径形成高亲和力。 IL-5已被证明是粘膜免疫系统的重要细胞因子，它具有几种免疫学特征，这些特征将其与系统性免疫室区分开。例如，IgA诱导时间（例如肠道相关的淋巴组织（GALT）或PEYER的斑块（PP），含有高频IgA commanted B细胞[表面IGAII D1+IE D1（Sigaii D1+IE D1+IE D1）B细胞和Th1/Th2细胞与lam ram ram igaiNAPINATINAL IMPRIRIAS IPRIANES ICAINARE INSINAL CORPRIAINAL CORPRIANES互联面（通过常见的粘膜免疫系统（CMI）。 IL-5是一种主要的细胞因子，可诱导…更多的S Sigaii D1+IE D1 B细胞，将主要使用PP和有丝分裂原刺激的脾B细胞的体外系统分化为产生IgA的血浆细胞。进一步的IL-2和IL-6已被证明能够在体外增强IgA合成。一个有趣的观察结果是，在鼠肠层中，多达40％的Iga产生细胞是由源自腹膜腔的B-1前体产生的。已经证明，腹膜和椎板PRAMINA B-1细胞已被证明是从公共池发育的，可能代表与常规PP B细胞分离的谱系。这些结果表明，B -1细胞可能是粘膜组织中产生IgA细胞的重要来源。我们将研究重点放在探索IL-5R和B-1细胞在粘膜相关组织中使用后一种基因脱离的鼠模型以及背景野生型小鼠的作用以及IL-5Rα在VIVO中选择性影响IL-5Rα的局部性。虽然IL-5RαILD1 - / - IE D1小鼠中粘膜分泌中的IgA水平比野生型小鼠更为r脉，但血清中的IgA水平没有改变。 frequency of IgA-producing cells was reduced in mucosal effector sites (e.g. intestinal lamina propria and nasal passage) but not in inductive sites such as PP and nasal-associated lymphoreticular, tissues (NALT) in IL-5RαII D1-/-IE D1 mice IgA-committed (surface IgAii D1+IE D1; sIgAii D1+IE D1）B-1细胞主要居住在粘膜效应部位，而常规的Sigaii D1+IE D1 B（B-2）细胞在野生型小鼠的粘膜电感部位形成。相比之下，在电感位点中的IL-5RαD1 - / - IE D1小鼠的效应组织中，Sigai D1+IE D1 B-1细胞，但不是Sigai D1+IE D1 B-2细胞，显着降低。 IL-5Rα在Sigai D1+IE D1 B-1细胞上比IL-6R更表达，而IL-5Rα和IL-6R均在野生型小鼠中的Sigai D1+IE D1 B-2细胞上表达。 Sigaii D1+IE D1 B-1细胞用重组IL-5（IL-5）而不是体外IL-6产生高水平的IgA。综上所述，研究结果表明，IL-5/IL-5R信号传导途径对于常见的粘膜免疫系统（CMIS）独立的Sigaii D1+IE D1 B-1细胞的发育和粘膜效应效应组织中的IgA反应至关重要。较少的