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

白细胞介素-5（IL-5）主要由激活的T淋巴细胞和肥大细胞产生。它最初是由它的活动作为一个B细胞生长因子和一个IgA增强因子来识别的。IL-5受体（IL-5 R）两个不同的膜蛋白、α和β链的综合体。通过IL-5 R α的结合IL-5异常，β链形式与IL-5 R α的内部信号转换途径具有很高的亲和力。IL-5，哪些将被展示为粘液免疫系统的重要细胞因子，哪些将具有来自系统免疫部分的多种免疫学特征？例如， IgA inductive tissues sues such as gut-associated lymphoreticular tissue （GALT） or Peyer's patches （PP）包含IgA-committed B cells的高频率[surface IgA D1+ giga D1 （sIgA D1+ giga D1） B cells and Th 1/Th 2 cells are interconnected with IgA效应站点包括intestinal lamina propria （i-LP）通过common mucosal immune system （CMIS）。IL-5是一种主要的细胞因子。 ... More s sIgA D1+ s D1B cells to differentiate into IgA-producing plasma cells using mainly an in vitro system using PP and mitogen-stimulated splenic B cells。进一步的IL-2和IL-6已经被证明能够在体外具有增强的IgA合成。一种启发性的观察表明，在一个从周颈洞穴中提取出的穆林中度Lamina propria增加了40%的IgA细胞。Peritoneal和Lamina propria B-1细胞在老鼠中显然是从一个普通的游泳池开发出来的，并可能从传统的PP B细胞中表示一个分离的线路。These results sugest that B - 1 cells could be an important source for IgA-producing cells in mucosal tissues。我们在mucosa-associated tissues using the latter gene-disrupted murine model together with the background wild type mice。Deletion of IL-5 R？selectively influenced the mucosal IgA responses in vivo。在IL-5 R α-D1-/-D1老鼠比野生型老鼠中的IgA水平更高，血清中的IgA水平没有改变。IgA的频率-生产细胞在微生物效应器站点中减少了（如中度lamina propria和nasal passage），但不包括在IL-5 R α-D1-/-D1鼠IgA提交的inductive网站中的PP和nasal相关淋巴细胞、tissues （NALT）（surface IgA型D1+型D1 ; sIgAイD1+イエD1）B-1 cells mainly resided in mucosal effector tissues， while conventional sIgAイD1+イエD1B（B-2） cells formed in mucosal inductive sites of wild type mice。在对比中，IL-5 R α-D1-/-β-D1米、sIgA β-D1 + β-D1 B-1细胞，但在诱导站点上没有sIgA β-D1+ β-D1 B-2细胞，被显著地减少。IL-5 R？was more expressed on sIgA？D1+？D1B-1 cells than was IL-6 R， while both IL-5 R？and IL-6 R were expressed on sIgA？D1+？D1B-2 cells in wild type mice。sIgA D1+イエD1B-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-5 R signaling pathway is critically important for the common mucosal immune system （CMIS） independent sIgAイD1+イエD1B-1 cell Management and for IgA responses in mucosal effector tissues in vivo。Less（低）

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