A novel FcεRIβ-chain truncation regulates human mast cell proliferation and survival
A novel FcεRIβ-chain truncation regulates human mast cell proliferation and survival
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DOI：
10.1096/fj.10-158378
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发表时间：
2010-10-01
期刊：
影响因子：
4.8
通讯作者：
Bradding, Peter
中科院分区：
文献类型：
--
作者：
Cruse, Glenn;Kaur, Davinder;Bradding, Peter
肥大细胞通过高亲和力的IgE受体Fc epsilon RI依赖于IgE的激活而参与过敏反应。Fc epsilon RIβ链(MS4A2)在肥大细胞功能中的作用尚不完全清楚，尽管它起到了放大Fc epsilon RI依赖的信号的作用。我们证明了一种新的缺失外显子3的MS4A2截断片段在人类肥大细胞中的表达，称为MS4A2(Trunc)。MS4A2(Trunc)基因的表达受肥大细胞生长因子干细胞因子(SCF)的负调控，在SCF受体功能增强的人肥大细胞系HMC-1中未检测到其表达。与MS4A2不同，MS4A2(Trunc)不向细胞膜转运，而是与核膜结合。过表达MS4A2(Trunc)可诱导人肺肥大细胞死亡，并通过诱导G(2)期细胞周期停滞和细胞凋亡而显著抑制HMC-1细胞的增殖。因此，我们已经确定了MS4A2的一个新的剪接变异体，它可能在调节人类肥大细胞的增殖和生存方面发挥重要作用。这一发现表明，MS4A2基因具有多种作用，超出了对急性过敏反应的调节。通过了解其功能的调控机制，有可能在体内诱导其在肥大细胞中的表达，这可能导致更好地治疗肥大细胞增多症和哮喘等疾病。-Cruse，G.，Kaur，D.，Leland，M.，Bradding，P.一种新的Fc epsilon RIβ链截断调控人类肥大细胞的增殖和生存。FASE B J.24,4047-4057(2010)。Www.fasebj.org
Mast cells contribute to allergy through IgE-dependent activation via the high-affinity IgE receptor Fc epsilon RI. The role of the Fc epsilon RI beta chain (MS4A2) in mast cell function is not understood fully, although it serves to amplify Fc epsilon RI-dependent signaling. We demonstrate the expression of a novel MS4A2 truncation lacking exon 3 in human mast cells termed MS4A2(trunc). MS4A2(trunc) gene expression was regulated negatively by the mast cell growth factor stem cell factor (SCF), and its expression was not detected in the SCF receptor gain-of-function human mast cell line HMC-1. Unlike MS4A2, MS4A2(trunc) did not traffic to the cytoplasmic membrane but instead was associated with the nuclear membrane. Overexpression of MS4A2(trunc) induced human lung mast cell death and profoundly inhibited HMC-1 cell proliferation by inducing G(2)-phase cell cycle arrest and apoptosis. Thus, we have identified a novel splice variant of MS4A2 that might be important in the regulation of human mast cell proliferation and survival. This finding demonstrates that the MS4A2 gene has multiple roles, extending beyond the regulation of acute allergic responses. By understanding the mechanisms regulating its function, it might be possible to induce its expression in mast cells in vivo, which could lead to better treatments for diseases such as mastocytosis and asthma.-Cruse, G., Kaur, D., Leyland, M., Bradding, P. A novel Fc epsilon RI beta-chain truncation regulates human mast cell proliferation and survival. FASEB J. 24, 4047-4057 (2010). www.fasebj.org