肥大细胞(mast cell )在过敏炎症反应中起着中枢作用，IgE激活肥大细胞启动下游的信号级联反应，产生具有生物学功能的介质，包括许多趋化因子。我们研究发现，钙调磷酸酶Aβ亚基(CnAβ)调节IgE介导的肥大细胞内趋化因子CCL1的产生，且早期生长应答因子2（EGR2）可以直接调控CCL1的表达。为此，我们提出了“IgE介导肥大细胞内CnAβ-EGR2-CCL1信号通路”的假说。本课题拟利用CnAβ敲除小鼠模型，首先试验明确CnAβ在IgE介导的肥大细胞活化中的作用；并在此基础上深入研究CnAβ调控EGR2的分子机理，进而阐明CnAβ调控肥大细胞内CCL1产生的分子机制，完善肥大细胞内CnAβ-EGR2-CCL1信号通路的假说。该研究将有助于深入了解CnAβ在肥大细胞内的生物学功能，丰富肥大细胞炎症因子产生的信号调控理论，并为探究过敏性疾病防治靶标提供理论依据。

Mast cells play a central role in allergic inflammation and are activated through cross-linking of FcβRI receptor-bound IgE, initiating a signaling cascade resulting in production of biologically potent mediators, including chemokines. Our study found that calcineurin A subunit beta (CnAβ) regulates IgE-mediated CCL1 production by mast cells. Meanwhile, we have identified that the transcription factor early growth response 2 (EGR2) was critical for allergen-induced mast cell CCL1 production. So we raise a novel hypothesis: there is a " CnAβ-EGR2-CCL1" signaling pathway in mast cell. To confirm this hypothesis, in this study, we culture bone marrow-derived mast cells (BMMCs) from wild-type and CnAβ-knockout mice. Firstly, we examine the roles of CnAβ in IgE-dependent mast cell activation. Furthermore, we plan to explain how CnAβ regulates EGR2 expression. Lastly, we will try to characterize the mechanism of CnAβ regulates IgE-dependent mast cell CCL1 production, to complete CnAβ-EGR2-CCL1 signaling pathway. This study will help to further understand the biologic function of CnAβ in mast cell, will enlarge our knowledge of mast cell allergic mediators product mechanism, and will provide indications to the control of allergic diseases and the development of novel therapeutic modalities.