细胞因子释放综合征（CRS）是嵌合抗原受体T细胞(CAR-T)治疗的主要并发症。新近发现细胞因子和趋化因子在CRS发病中起重要作用。前期血清细胞因子芯片发现趋化因子XCL1在CRS高峰期明显升高，CD8+T和靶向CD19的CAR-T(CART19)为CRS主要效应细胞且细胞表面高表达XCL1，该细胞迁移至白血病部位并被活化释放细胞因子是CRS发生的直接原因。预实验表明，CRS模型中阻断XCL1能减轻CRS，提示XCL1在CRS中起重要作用。本项目先在CRS小鼠模型中利用XCL1阻滞剂和重组XCL1验证XCL1在CRS中的作用，利用细胞共培养阐明XCL1促进T细胞迁移的作用及机制，流式细胞术、免疫印迹等明确XCL1在CART19及CD8+T细胞经细胞因子介导的非特异性活化和DC细胞介导的特异性活化中的重要作用和机制，为阐明CRS发病机制提供实验依据，为发现CRS新型治疗靶点奠定基础。

Cytokine release syndrome (CRS) is the major complication after chimeric antigen receptor T cell (CART) therapy. Recent researches showed that cytokines and chemockines play important roles in CRS pathogenesis. In our previous research we found the serum level of chemockine XCL1 were greatly increased in CRS peak stage in constrast to that before CRS and CRS restoration, what's more, we found XCL1 expression in CD8+ T cells and CART19 cells were greatly increased. Migration and activation of the T cells were the direct causes of CRS. Our preliminary data found that XCL1 blockage can mitigate CRS implying that XCL1 played important roles in CRS pathogenesis. The current study will first verify XCL1 have important roles in CRS pathogenesis. Next we will clarify the roles and mechanisms of XCL1 in T cell migration via cell-cell co-culture. Finally the roles and mechanisms of XCL1 in T cell non-specific cell activation by cytokines and DC-mediated T cell specific activation were clarified. The research can lay the foundation for novel mechanisms of CAR-T associated CRS. And also the research will provide novel targets for CRS treatment.