脑源性GABA经非意念控制系统调控结肠癌免疫微环境的机制研究

非意念控制系统脑肠轴通路在肠道免疫微环境的调控及肠道肿瘤的发生发展过程中发挥着重要的作用。中枢神经系统功能紊乱通过非意念控制系统脑肠轴通路影响肠道肿瘤的发生发展，肠道免疫微环境紊乱作为肿瘤的重要特征，在该过程中发挥重要的作用。本课题组前期研究发现，中枢神经系统功能紊乱引起脑源性GABA异常表达，肠神经和肠道固有免疫细胞（ILC3）间紧密接触减少，IL-22肠道表达升高。IL-22主要来源于ILC3，IL-22可以增强结肠肿瘤的增殖、迁移等能力。因此申报者推测，脑源性GABA经非意念控制系统调控肠道ILC3释放IL-22，进而参与结肠癌的发生发展。本项目拟借助腺相关病毒脑定位注射、基因敲除小鼠等技术，探索脑源性GABA经非意念控制系统调控肠道ILC3释放IL-22，进而参与结肠癌的发生发展的具体机制，为通过调控中枢神经系统功能干预结肠癌的进程提供新的理论依据。

The involuntary control system brain-gut axis pathway plays an important role in the regulation of the intestinal immune microenvironment and the occurrence and development of intestinal tumors. Central nervous system dysfunction regulates the intestinal endocrine and immune microenvironment through unintentional control system brain-gut axis pathways, affecting the occurrence and development of intestinal tumors, intestinal immune microenvironment disorder plays an important role in this process as an important feature of tumors. Our previous study found that central nervous system dysfunction caused abnormal expression of brain-derived γ-aminobutyric acid (GABA) and decreased close contact between enteric nerves and intestinal innate immune cells (ILC3). IL-22 is mainly derived from ILC3. IL-22 can enhance the ability of colon tumors to proliferate and migrate. Therefore, we speculates that brain-derived GABA regulates the release of IL-22 from intestinal ILC3 through the involuntary control systems, and then participates in the development of colon cancer. This project intends to use adeno-associated virus brain localization injection, gene knockout mice and other technologies to explore the specificity of brain-derived GABA through involuntary control systems to regulate the release of IL-22 from intestinal ILC3 and further participate in the development of colon cancer The mechanism provides a new theoretical basis for intervening the progress of colon cancer by regulating central nervous system function.