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

经常观察到嗜碱性粒细胞募集到过敏性炎症部位。然而，没有确切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关键作用。嗜碱性粒细胞占外周血白细胞的不到1%。并且经常被认为是次要的和可能多余的“循环肥大细胞”。在这项研究中，我们已经证明，嗜碱性粒细胞发挥重要的和非冗余的作用，并负责IgE介导的慢性过敏性炎症的发展，独立于T细胞和肥大细胞。单次皮下注射多价抗原不仅引起立即和晚期耳肿胀，而且在抗原特异性IgE和IgE转基因小鼠致敏的小鼠中引起延迟发作的耳肿胀伴大量嗜酸性粒细胞浸润。肥大细胞是必不可少的即时和后期的耳肿胀，但延迟的一个。T细胞也为后者所抑制。在Fcε RI缺陷小鼠中未发生迟发型过敏性炎症，但通过从正常小鼠中转移表达Fcε RI的嗜碱性粒细胞，这些小鼠中的迟发型过敏性炎症得以恢复。这些发现提示嗜碱性粒细胞通过抗原、IgE和FcεRI的相互作用诱导慢性变应性炎症发展的新机制。目前的研究表明，嗜碱性粒细胞及其产物可能是治疗这种类型的慢性过敏性炎症的良好靶点。

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.