IL-21 administration into the nostril alleviates murine allergic rhinitis
IL-21 administration into the nostril alleviates murine allergic rhinitis
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DOI：
10.4049/jimmunol.179.10.7157
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Mazda, Osam
中科院分区：
文献类型：
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作者：
Hiromura, Yayoi;Kishida, Tsunao;Mazda, Osam
I型变应性疾病如变应性鼻炎是由IgE介导的体液免疫反应引起的，而嗜酸性粒细胞在IgE介导的变态反应的病因学中也发挥重要作用。IL-21调节T、B和NK细胞的生长、分化和功能，而IgE的产生也受IL-21的影响。在这项研究中，我们研究了IL-21是否能够控制IgE介导的过敏反应，在体内使用过敏性鼻炎小鼠模型，建立了反复致敏和鼻内攻击与OVA。鼻内给药重组小鼠IL-21（rmIL-21）显着减少打喷嚏的次数，以及OVA特异性IgE的血清浓度，与未处理的过敏小鼠相比。rmIL-21处理还抑制了鼻相关淋巴组织中的生殖细胞C β转录，这可能至少部分是由于IL-21引起的Bcl-6 mRNA的上调。局部表达的IL-4，IL-5和IL-13也被抑制的鼻内细胞因子治疗，而相反，内源性IL-21 mRNA的表达诱导外源性rmIL-21。此外，IL-21作用于鼻成纤维细胞以抑制嗜酸性粒细胞趋化因子的产生。IL-21的这种新功能可能与组织病理学观察显示的嗜酸性粒细胞浸润到鼻粘膜中的减弱有关。这些结果表明，IL-21鼻内给药通过多效性活性有效地改善了变应性鼻炎，即，阻止B细胞产生IgE和成纤维细胞产生嗜酸性粒细胞趋化因子。
Type I allergic diseases such as allergic rhinitis are caused by IgE-mediated humoral immune responses, while eosinophils also fulfill important roles in the etiology of IgE-mediated allergy. IL-21 regulates growth, differentiation, and function of T, B, and NK cells, while the production of IgE is also influenced by IL-21. In this study we examined whether IL-21 is capable of controlling IgE-mediated allergic reactions in vivo by using the allergic rhinitis mouse model that was established by repetitive sensitization and intranasal challenge with OVA. Intranasal administration with recombinant mouse IL-21 (rmIL-21) significantly reduced the number of sneezes, as well as the serum concentration of OVA-specific IgE, in comparison with that of untreated allergic mice. The rmIL-21 treatment also suppressed germline C epsilon transcription in the nasal-associated lymphoid tissues, which may have, at least partly, resulted from the up-regulation of Bcl-6 mRNA caused by IL-21. Local expression of IL-4, IL-5, and IL-13 was also inhibited by the intranasal cytokine therapy whereas, in contrast, the expression of endogenous IL-21 mRNA was induced by exogenous rmIL-21. Moreover, IL-21 acted on nasal fibroblasts to inhibit production of eotaxin. This novel function of IL-21 may be associated with the attenuation of eosinophil infiltration into nasal mucosa that was revealed by histopathological observation. These results indicated that IL-21 nasal administration effectively ameliorated allergic rhinitis through pleiotropic activities, i.e., the prevention of IgE production by B cells and eotaxin production by fibroblasts.