CD169+巨噬细胞通过活化CCR7/CCR8通路诱导树突细胞迁移在变应性鼻炎中的作用研究

CD169+巨噬细胞（MФ）是一群新定义的巨噬细胞亚群，与其他细胞通过相关配体识别并结合，在抗原递呈、免疫耐受等反应中发挥重要作用。有报道称在变态反应中CD169+MФ可诱导树突细胞（DCs）迁移到次级淋巴组织，促使Th0向Th2分化，但具体机制不清。我们前期研究发现，变应性鼻炎（AR）小鼠鼻黏膜中CD169+MФ和Th2炎症相关DCs（cDC2）增多，CCR7和CCR8通路同时活化。选择性剔除CD169+MФ后，cDC2明显减少，Th2炎症改善。因此，我们推测AR小鼠鼻黏膜中CD169+MФ可能通过激活CCR7和CCR8通路，诱导cDC2迁移至黏膜固有层，促进炎症向Th2分化，导致CD4+Th细胞网络失衡。在本研究中，我们拟采用单细胞测序、流式分选等技术，明确AR小鼠鼻黏膜中CD169+MФ的表型特征，及其促进DC迁移和Th2分化的具体调控机制，揭示AR中免疫调控新机制。

CD169+ macrophages (MФ) is a new kind of subpopulation of macrophages, which can recognize or bind with other cells through related ligands, and plays an important role in antigen presentation, immune tolerance and other responses. It has been reported that CD169+MФ can induce dendritic cells (DCs) to migrate to secondary lymphoid tissues in allergic reactions and promote Th0 to Th2 differentiation, but the mechanism is unclear. Our previous studies found that CD169+MФ and the DCs，which are related to Th2 inflammation（cDC2），increased in the nasal mucosa of allergic rhinitis (AR) mice, and the CCR7 and CCR8 pathways were activated simultaneously. After elimination of CD169+MФ, cDC2 were significantly reduced and Th2 inflammation was improved. Therefore, we speculated that CD169+MФ in the nasal mucosa may induce the migration of cDC2 to the lamina propria by activating the CCR7 and CCR8 pathways, and promote the differentiation of Th2 inflammation through related cytokines and co-stimulatory molecules, leading to an imbalance in the CD4+Th cell network. In this study, we intend to use single cell sequencing, flow sorting, and other technologies to clarify the phenotypic characteristics of CD169+MФ in the nasal mucosa of mice and their specific regulatory mechanisms for DCs migration and Th2 differentiation, in an attempt to reveal the new mechanism of local immune regulation of nasal mucosa in AR.