Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy
Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy
复制标题
DOI：
10.1073/pnas.1608520113
复制
发表时间：
2016-12-06
影响因子：
11.1
通讯作者：
Metcalfe, Dean D.
中科院分区：
文献类型：
--
作者：
Cruse, Glenn;Yin, Yuzhi;Metcalfe, Dean D.
过敏性疾病是由肥大细胞的激活和针对 IgE 定向抗原的介质释放引起的。然而，目前还没有药物可以在长期给药时特异性下调体内肥大细胞功能。在这里，我们描述了一种在体外和体内靶向肥大细胞的创新方法，利用反义寡核苷酸介导的高亲和力 IgE 受体 (Fc epsilon RI beta) β 亚基的外显子跳跃来消除表面高亲和力 IgE 受体 (Fc epsilon RI) 的表达和功能，使肥大细胞对 IgE 介导的激活无反应。由于 Fc epsilon RI beta 表达仅限于肥大细胞和嗜碱性粒细胞，因此该方法将选择性地针对这些细胞类型。鉴于外显子跳跃在治疗杜氏肌营养不良等遗传性疾病的临床试验中取得了成功，我们提出 Fc epsilon RI beta 的外显子跳跃是肥大细胞特异性治疗过敏性疾病的潜在方法。
Allergic diseases are driven by activation of mast cells and release of mediators in response to IgE-directed antigens. However, there are no drugs currently available that can specifically down-regulate mast cell function in vivo when chronically administered. Here, we describe an innovative approach for targeting mast cells in vitro and in vivo using antisense oligonucleotide-mediated exon skipping of the beta-subunit of the high-affinity IgE receptor (Fc epsilon RI beta) to eliminate surface high-affinity IgE receptor (Fc epsilon RI) expression and function, rendering mast cells unresponsive to IgE-mediated activation. As Fc epsilon RI beta expression is restricted to mast cells and basophils, this approach would selectively target these cell types. Given the success of exon skipping in clinical trials to treat genetic diseases such as Duchenne muscular dystrophy, we propose that exon skipping of Fc epsilon RI beta is a potential approach for mast cell-specific treatment of allergic diseases.