组织微环境特定新型免疫细胞亚群的发现与定居机制的交叉研究

基质微环境和免疫细胞的相互作用是区域免疫的重要科学问题，其中发现组织特定新型亚群和组织定居机制是区域免疫的研究热点。研究体内组织微环境中的免疫和基质细胞需要特异性的靶向技术，但现有示踪模型很难特异性的追溯和清除特定组织中定居细胞。建立这种溯源性地研究某一组织定居细胞，基于定居机制和组织特异性分子的发现，结合纳米技术和条件性示踪动物模型的发展，可能为该技术研制带来新机遇。本项目基于单细胞测序，研究肺和皮肤新型免疫细胞亚群、基质细胞对免疫细胞的调控、组织定居机制，基于此建立条件示踪肺和皮肤组织细胞的纳米技术和模型动物，利用它们研究肺癌和银屑病中组织免疫细胞的定居属性、迁移路径、在再分布组织的免疫特性。研究结果有助于更新现有认识、深入解析肺和皮肤的免疫属性，和疾病的病理机制，也为认识区域免疫与系统免疫的交互作用和靶向组织器官治疗疾病提供理论依据和技术支撑。

The interaction between stromal cells and immune cells is an important scientific problem in original immunity, among which discoveries of novel tissue-resident subsets and tissue-resident mechanisms are research hotspots. Some of immune hypothesis from splicing fragmented researches may be biased from real physiological or pathogenic processes. Fate-mapping models are ideal research techniques to trace certain tissue-resident immune cells and study their tissue-resident and immune features. Discoveries of tissue-resident mechanisms and tissue-specific molecules are benefit of making a breakthrough in such fate-mapping techniques, such as novel tracing nanotechnologies and conditional fate-mapping models. The project is focused on lung and skin tissue microenvironment and based on single cell-sequencing technology and bioinformatic analysis to discover novel immune cell subsets or stromal cells, the effects of stromal cells on immune cells, tissue-resident mechanisms and tissue-specific molecules. Based on tissue-resident or tissue-specific molecules to establish conditional fate-mapping models and nano-tracing techniques which are utilized to further investigate the changes of tissue-resident and immune features of tissue immune cells and their migration route, redistribution, immune features and roles of tissue immune cells after migration in lung-tumor or psoriasis models. The study is helpful to understand tissue-resident mechanism and immune features of lung or skin, pathogenic mechanisms of diseases, and the interactions between lung or skin original immunity and systemic immunity, and also provide technical supports for studying the biological features of tissue-resident cells after migration and targeting tissues immunotherapy.