Hiromura Yayoi, Kishida Tsunao, Nakano Hiroshi, Hama Takemitsu, Imanishi Jiro, Hisa Yasuo, Mazda Osam
Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
J Immunol. 2007 Nov 15;179(10):7157-65. doi: 10.4049/jimmunol.179.10.7157.
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 Cepsilon 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.
I型过敏性疾病如过敏性鼻炎是由IgE介导的体液免疫反应引起的，而嗜酸性粒细胞在IgE介导的过敏病因中也发挥着重要作用。白细胞介素-21（IL-21）调节T细胞、B细胞和自然杀伤细胞（NK细胞）的生长、分化和功能，同时IgE的产生也受IL-21影响。在本研究中，我们通过用卵清蛋白（OVA）反复致敏和鼻内激发建立过敏性鼻炎小鼠模型，来检测IL-21是否能够在体内控制IgE介导的过敏反应。与未治疗的过敏性小鼠相比，鼻内给予重组小鼠IL-21（rmIL-21）可显著减少喷嚏次数以及OVA特异性IgE的血清浓度。rmIL-21治疗还抑制了鼻相关淋巴组织中种系Cε转录，这可能至少部分是由IL-21引起的Bcl-6 mRNA上调所致。鼻内细胞因子治疗也抑制了白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和白细胞介素-13（IL-13）的局部表达，而相反，外源性rmIL-21可诱导内源性IL-21 mRNA的表达。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的这一新功能可能与组织病理学观察显示的嗜酸性粒细胞向鼻黏膜浸润的减轻有关。这些结果表明，鼻内给予IL-21通过多效性活动有效改善了过敏性鼻炎，即预防B细胞产生IgE和成纤维细胞产生嗜酸性粒细胞趋化因子。
