Allergen-independent immunomodulatory activities of immunoglobulin E.
Allergen-independent immunomodulatory activities of immunoglobulin E.
复制标题
免疫球蛋白 E 具有独立于过敏原的免疫调节活性。
DOI：
10.1111/j.1365-2222.2008.03182.x
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kawakami,T
中科院分区：
文献类型：
--
作者：
Horner,AA;Kawakami,T
1966年，IgE被确定为介导I型超敏反应的主要抗体[1]。这种分子洞察开创了我们对过敏性疾病理解的新时代。最近，人们发现 IgE 分子也具有过敏原依赖性免疫调节活性。在本月的《临床和实验过敏》杂志中，Mathias 博士及其同事证明，循环 IgE 会影响小鼠对吸入半抗原敏感的能力 [2]。这一观察结果与之前的研究一致，证明 IgE 具有不受过敏原交联介导的免疫调节活性。未来的研究需要确定 IgE 独立于过敏原的免疫调节活性的机制及其对人类健康和疾病的影响。据报道，在 20 世纪 70 年代，受试者血清中的总 IgE 水平与其嗜碱性粒细胞上的高亲和力 IgE 受体 (FcεRI) 表达水平相关 [3]，Furuichi 等人。 20 世纪 80 年代，RBL-2H3 大鼠肥大细胞与 IgE 一起孵育可增强其 FcεRI 表达 [4]。两个实验室在 90 年代中期进一步证实血清 IgE 直接调节肥大细胞 FcεRI 表达 [5, 6]。从功能上讲，已发现 FcεRI 与 IgE 的结合可以启动肥大细胞，从而在 IgE 交联时增强颗粒释放和细胞因子产生 [7]。除了 FcεRI 之外，血清 IgE 已被证明可以调节其低亲和力受体 CD23 的表达 [8, 9]。例如，虽然所有 B 细胞都表达 CD23，但野生型小鼠 B 细胞的表达水平远高于 IgE 缺陷小鼠的 B 细胞。此外，向 IgE 缺陷小鼠注射 IgE 会导致 B 细胞 CD23 表达增加。有趣的是，与野生型小鼠相比，CD23 缺陷小鼠的血清 IgE 水平较高，而 CD23 转基因小鼠的 IgE 水平较低，这表明 CD23 信号传导有助于调节 IgE 的产生 [10, 11]。
In 1966, IgE was identified as the principal antibody responsible for mediating the type I hypersensitivity response [1]. This molecular insight ushered in a new era in our understanding of allergic diseases. More recently, it has come to light that IgE molecules also have allergenindependent immunomodulatory activities. In this month’s issue of Clinical and Experimental Allergy, Dr Mathias and colleagues demonstrate that circulating IgE impacts on the ability of mice to become sensitized to an inhaled hapten [2]. The observation is consistent with previous studies in demonstrating that IgE has immunomodulatory activities that are not mediated by allergen cross-linking. Future studies will need to determine the mechanisms underlying IgE’s allergen-independent immunomodulatory activities and their impact on human health and disease.The level of total IgE in a subjects serum was reported to correlate with the level of high affinity IgE receptor (FcεRI) expression on their basophils [3] in the 1970s, and Furuichi et al. went on to demonstrate that incubation of RBL-2H3 rat mast cells with IgE enhances their expression of FcεRI [4] in the 1980s. Two laboratories further established that serum IgE directly regulates mast cell FcεRI expression in the mid-90s [5, 6]. Functionally, IgE engagement of FcεRI has been found to prime mast cells for enhanced granule release and cytokine production upon IgE cross-linking [7]. In addition to FcεRI, serum IgE has been shown to regulate the expression of its low affinity receptor, CD23 [8, 9]. For example, while all B cells express CD23, expression levels are far higher on B cells from wild-type mice than on B cells from IgE-deficient mice. Moreover, injection of IgE into IgE-deficient mice leads to increased B cell CD23 expression. Interestingly, CD23-deficient mice have higher serum IgE levels and CD23 transgenic mice have lower IgE levels than wild-type mice, suggesting that CD23 signaling helps to regulate IgE production [10, 11].