蛋白酪氨酸磷酸酶SHP1对间充质干细胞免疫调节特性的作用及其机制研究

间充质干细胞（MSCs）作为一种多潜能干细胞，存在于多种组织中，具有免疫调节功能，参与肿瘤、炎症性疾病等诸多免疫反应。然而，目前调控MSCs免疫调节特性的机制仍不清楚。Src Homology domain-containing phosphatase-1（SHP1）作为蛋白酪氨酸磷酸酶，参与调控细胞增殖、分化、活化等过程，与体内许多病理生理现象相关。研究发现巨噬细胞和神经胶质细胞中SHP1抑制一氧化氮（NO）的产生。由于NO是介导MSCs免疫调节特性关键的效应分子，因此，我们提出假设SHP1调控MSCs免疫调节特性以及该调控作用参与肿瘤的发生发展。本课题拟阐明SHP1对MSCs免疫调节特性的调控作用及其分子机制，阐述SHP1调控MSCs免疫调节特性与肿瘤发生发展的联系；将拓展对MSCs免疫调节特性调控机制的认识，为阐明MSCs与肿瘤的关系提供科学依据，为MSCs在肿瘤治疗中提供理论指导。

Mesenchymal stem cells (MSCs) are multiple stem cells existing in various tissues. They possess immunomodulatory ability and participate in various immune reaction, such as tumor, inflammatory diseases and so on. However, the detailed mechanisms controlling the immunomodulatory property of MSCs are still elusive. Src Homology 2 (SH2) domain-containing phosphatase-1 (SHP1) is a member of the protein–tyrosine phosphatase (PTP) family, which regulates processes including cell growth, proliferation and activation, closely related with various pathological and physiological processes. Previous reports found that in macrophages and neuroglia cells SHP1 blocked nitric oxide (NO) production, which is a key effector molecule in mediating MSC immunomodulatory property. Therefore, we hypothesize that SHP1 regulates the immunomodulatory property of MSCs, which plays a key role in tumor progression. We are aimed to explore the regulation and mechanism of MSC immunomodulatory property by SHP1, and explain the relation with tumor progression. This project will expand our awareness of the mechanism regulating MSC immunomodulatory property, provide important scientific basis for explaining the relation of MSCs with tumor, and furnish theoretical guidance for clinical MSC treatment in tumor.