下调CCR3基因抑制CD4+T细胞向Th2分化在变应性鼻炎中的作用及机制研究

CD4+T细胞分化为TH2细胞影响TH1/TH2的平衡，CCR3可促进TH2细胞的极化并促使TH2细胞因子的释放,而此过程与IL-4/IL-13/STAT6信号密切相关。我们前期研究（已发SCi及中华核心）及预实验发现：沉默CCR3可抑制EOS及肥大细胞的迁移和脱颗粒作用，并抑制鼻粘膜相关TH2细胞因子表达。但是下调CCR3是否可抑制CD4+T细胞向Th2细胞分化,具体机制如何?目前尚未明确。基于文献报道和我们前期的研究结果，提出如下假设：下调CCR3将抑制CD4+T细胞向TH2细胞的分化进而抑制Th2应答反应，该机制可能借助阻断IL-4/IL-13/STAT6信号通路而发挥作用。我们将通过RNAi技术，采用磁珠分选、细胞培养、ELISA及PCR等手段，从分子、细胞、组织及动物整体水平多方面探讨该方法在变应性鼻炎发病中的作用及机制,为CCR3作为靶基因应用于变应性鼻炎的治疗打下理论基础。

The differentiation of CD4 + T cells into TH2 cells affects the balance of TH1 / TH2. CCR3 can promote the polarization of TH2 cells and the release of TH2 cytokines, and this process is closely related to IL-4 / IL-13 / STAT6 signaling. Our previous research (sent SCi and Chinese core) and preliminary experiments found that silencing CCR3 can inhibit the migration and degranulation of EOS and mast cells, and inhibit the expression of nasal mucosa-related TH2 cytokines. But whether down-regulation of CCR3 can inhibit the transformation of CD4 + T cells to Th2 cells, what is the specific mechanism? It is not clear yet. Based on the literature reports and our previous research results, the following hypothesis is proposed: down-regulation of CCR3 will inhibit the differentiation of CD4 + T cells into TH2 cells and thus inhibit the Th2 response. This mechanism may be by blocking the IL-4 / IL-13 / STAT6 signaling pathway And play a role. We will use RNAi technology, magnetic bead sorting, cell culture, ELISA and PCR to explore the role and mechanism of this method in the pathogenesis of allergic rhinitis from the aspects of molecules, cells, tissues and animals as a whole. It will build a theoretical foundation for the treatment of allergic rhinitis for CCR3 as a target gene.