Role of IL/25 in the regulation of allergic airway inflammation

近年来，通过数据库检索发现了与IL-17同源的细胞因子。发现了5个新的家族成员，分别是IL-17B、IL-17C、IL-17D、IL-17E/IL-25和IL-17F，这些分子与IL-17具有18-30%的同源性。在IL-17家族细胞因子中，研究表明IL-25的体内和体外生物活性与IL-17和其他IL-17家族细胞因子有显著不同。IL-25的表达通过从未知的非t细胞群中产生IL-5导致嗜酸性粒细胞的扩增，而其他IL-17家族细胞因子诱导中性粒细胞的扩增。此外，IL-25在多种组织中诱导IL-4和IL-13基因表达升高，从而引起th2型免疫反应，包括血清IgE水平升高和嗜酸性粒细胞浸润的病理改变。在本研究中，我们首次证明肥大细胞也是有效的il -25产生细胞。我们发现，当IgE交联刺激骨髓源性肥大细胞（BMMCs）时，IL-25 mRNA在30分钟内以钙调磷酸酶依赖的方式被诱导，IL-25 mRNA的水平与活化的Th2细胞相当。通过免疫印迹法在蛋白水平上检测肥大细胞产生IL-25。我们还研究了IL-25在变应性气道炎症中的作用。我们发现IL-25 mRNA在吸入致敏小鼠气道中被诱导。此外，在CC10-IL-25转基因小鼠中，IL-25在肺部的强化表达导致抗原诱导的气道炎症增强。这些结果提示IL-25参与变应性气道炎症的增强。

Recently, cytokines homologous to IL-17 have been identified by database searching. Five new family members have been identified, namely IL-17B,IL-17C,IL-17D,IL-17E/IL-25,and IL-17F, in which these molecules possess 18-30% homology to IL-17. Among IL-17 family cytokines, it has been shown that the in vivo and in vitro biological activities of IL-25 are markedly different from those described for IL-17 and other IL-17 family cytokines. The expression of IL-25 results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T cell population, whereas other IL-17 family cytokines induce the expansion of neutrophils. In addition, IL-25 induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant Th2-type immune responses, including increased serum IgE levels and pathological changes with eosinophilic infiltrates.In the present study, we first show that mast cells are also potent IL-25-producing cells. We found that when bone marrow-derived mast cells(BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min in a calcineurin-dependent manner and the levels of IL-25 mRNA were comparable to that of activated Th2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting.We also investigated the role of IL-25 in allergic airway inflammation. We found that IL-25 mRNA was induced in the airways in the sensitized mice upon the inhaled allergen challenge. Moreover, the enforced expression of IL-25 in the lung in CC10-IL-25 transgenic mice resulted in the enhanced antigen-induced airway inflammation. These results suggest that IL-25 is involved in the enhancement of allergic airway inflammation.