Identification of Critical Signaling Pathways Modulating Mast Cell Activation

肥大细胞在哮喘和其他过敏性疾病的发病机制中起着关键作用。这些反应通常是由表达在细胞表面的高亲和力IgE受体（Fc-epsilon-RI）的抗原依赖性聚集和随后的促炎介质（如组胺、前列腺素、蛋白酶和细胞因子）的释放引起的。然而，其他受体的配体，如KIT和各种gpcr，可以作为抗原介导的肥大细胞激活的起始肥大细胞，或作为辅助激活剂。连接Fc-epsilon-RI聚集与人类肥大细胞激活和功能的信号通路以及其他受体如何修饰这些fc介导的信号通路尚不清楚。因此，本研究的主要重点是阐明与通过Fc-epsilon-RI激活肥大细胞相关的信号机制，特别是由其他受体启动的信号通路如何与Fc-epsilon-RI启动的信号通路整合，以协同肥大细胞激活和/或抑制肥大细胞。

Mast cells play a pivotal role in the pathogenesis of asthma and other allergic diseases. These reactions are generally initiated by antigen-dependent aggregation of the high affinity IgE receptor (Fc-epsilon-RI) expressed on the cell surface and subsequent release of pro-inflammatory mediators (e.g. histamine, prostanoids, proteases and cytokines). However, ligands for other receptors such as KIT and various GPCRs may serve to prime mast cells for, or act as co-activators of, antigen-mediated mast cell activation. The signaling pathways linking Fc-epsilon-RI aggregation to human mast cell activation and function and how other receptors modify these Fc-mediated signaling events is unclear. Thus the primary focus of the research is the elucidation of signaling mechanisms associated with the activation of mast cells via the Fc-epsilon-RI and especially how the signaling pathways initiated by other receptors may integrate with those initiated by the Fc-epsilon-RI for synergistic mast cell activation and/or inhibition. The ability of mast cells to impact disease states in vivo also depends on their growth and differentiation from their progenitor cells, migration of the mast cells to their resident tissues, and survival at these sites. Therefore the integrated receptor-mediated signaling events regulating these processes are also being examined.