Study on a novel mechanism by which IgE/FcεRI mediates chronic allergic inflammation

经常可以观察到嗜碱性粒细胞聚集到变态反应性炎症部位。然而，还没有提供确凿的证据表明嗜碱性粒细胞在慢性变态反应性疾病的发病机制中起着至关重要的作用。嗜碱性粒细胞在外周血白细胞中所占比例不到1%。通常被认为是微小的、可能是多余的“循环肥大细胞”。在这项研究中，我们证明了嗜碱性粒细胞在免疫球蛋白E介导的慢性变态反应性炎症的发展中起着重要的和非多余的作用，而不依赖于T细胞和肥大细胞。单次皮下注射多价抗原不仅会引起即刻和晚期的耳肿胀，而且在抗原特异性IgE和IgE转基因小鼠致敏的小鼠中，还会出现延迟性耳肿胀和大量嗜酸性粒细胞浸润。肥大细胞对于即刻和晚期的耳朵肿胀是必不可少的，但对于延迟的耳朵肿胀是必不可少的。T细胞对于后者也是可有可无的。FcεRI缺陷小鼠未出现迟发性变态反应性炎症，但通过转移表达FcεRI的正常小鼠的嗜碱性粒细胞，这些小鼠的迟发性变态反应性炎症得到恢复。这些发现提示了一种新的慢性变态反应性炎症的发生机制，即由嗜碱性粒细胞通过抗原、Ig E和FcεRI的相互作用而诱导的。目前的研究表明，嗜碱性粒细胞及其产品可能是治疗这种类型的慢性变应性炎症的良好靶点。

The recruitment of basophils into the sites of allergic inflammation is often observed. However, no definitive evidence has been provided that basophils are crucially involved in the pathogenesis of chronic allergic disorders. Basophils represent less than 1% of peripheral blood leukocytes. and have often been considered as minor and possibly redundant "circulating mast cells". In this study, we have demonstrated that basophils play an important and non-redundant role and are responsible for the development of IgE-mediated chronic allergic inflammation, independently of T cells and mast cells. A single subcutaneous injection of multivalent antigens elicited not only immediate- and late-phase ear swelling but also delayed-onset ear swelling with massive eosinophil infiltration in mice sensitized with antigen-specific IgE and IgE transgenic mice. Mast cells were essential for the immediate- and late-phase ear swelling but dispensable for the delayed one. T cells were also dispensable for the latter. The delayed-onset allergic inflammation was not developed in FcεRI-deficient mice, but it was restored in these mice by transferring FcεRI-expressing basophils from normal mice. These findings indicate a novel mechanism of development of chronic allergic inflammation that is induced by basophils through the-interaction of antigen, IgE, and FcεRI. The present study implies that basophils and their products could be good targets to treat this type of chronic allergic inflammation.