急性B淋巴细胞白血病（ALL）中Treg细胞及Nrp-1发挥重要作用，前期研究发现抗体阻断Nrp-1功能可导致小鼠肿瘤环境中Treg数量增加，而IL-10可调节Nrp-1的表达，且Nrp-1可与PDX1结合。据此，我们提出假设：IL-10可能通过上调Nrp-1表达及其与PDX1的结合来增加Treg细胞数量进而促进ALL的发生及发展。本项目拟在前期基础上，利用NALM-6-UM1白血病细胞系以及从临床样本中分离出ALL病人肿瘤细胞分别建立CDX和人源化PDX小鼠模型，模拟人体内肿瘤微环境，研究IL-10调节Nrp-1表达的分子机制及Nrp-1与PDX1结合对FoxP3转录及Treg细胞生成的影响，明确干预Nrp-1的功能对ALL发生及发展的影响，该项目的实施可以为阐明ALL发生机制、研制基于Nrp-1的嵌合型Car-T靶点治疗白血病并抑制细胞因子风暴的免疫治疗提供理论基础。

Regulatory T （Treg）cells and Neuropilin-1(Nrp-1) play an important role in Acute B lymphocytic leukemia (ALL) disease. Previous research, we found that neutralizing antibody of Nrp - 1 increased the number of Treg cells in tumor environment while the expression of Nrp-1 regulated by IL-10 which combined with PDX1. On this basis, we hypothesized that IL-10 plays its function through increased the number of Nrp-1 and its combination with PDX1 to increase the quantity of Treg cells and promote the development of ALL progressed. This project plans to use NALM-6-UM1 myelogenous leukemia cell lines and isolate tumor cells of ALL patients from clinical samples to establish CDX and humanized PDX mouse models, to simulate the human tumor microenvironment through isolated tumor cells from clinical samples to investigate the molecular mechanism of IL-10 regulates Nrp-1 expression and the function of Nrp-1 binding with PDX1 to regulate FoxP3 transcription and Treg cell formation ,and explicit of intervention Nrp-1 how to influence ALL disease development. Implementation of this project will clarified the pathogenesis of ALL which is advanced to develop a chimeric type Nrp-1-Car-T Targets to therapy leukemia and inhibiting cytokine storm to provide theoretical basis.