系统性红斑狼疮（systemic lupus erythematosus, SLE）的T细胞免疫已成为研究热点，然而辅助性T细胞17（T helper type 17, Th17）在SLE中的功能尚未明确；趋化因子Fractalkine/ CX3CL1（FKN）可吸引T细胞的高效抗原呈递，FKN受体CX3CR1缺陷可通过减少Th17细胞反应实现对炎症的保护作用，但在FKN通过Th17细胞调控SLE方面的研究有待于进一步深入；本项目拟以CRISPR/Cas9基因组编辑技术，研究狼疮小鼠CD4+ T细胞过表达和缺陷表达FKN对Th17细胞活化的影响，以狼疮小鼠、基因敲除小鼠作为研究模型，探讨FKN通过活化Th17细胞对SLE的调控机制，阐明FKN拮抗可否通过调控Th17细胞功能来治疗SLE，并发现参与此过程的细胞因子和信号通路，研究将有助于理解SLE发病机理及开发靶向治疗药物。

T cell immunity in systemic lupus erythematosus (SLE) has become increasingly appreciated. T helper 17 (Th17) cells are a unique CD4+ T subset characterized as preferential producers of interleukin-17 (IL-17). However, the function of Th17 cells in SLE is indefinite. Fractalkine/CX3CL1 (FKN), the unique member of the CX3C chemokine family, mediates both chemotaxis and adhesion of inflammatory cells via its highly selective receptor CX3CR1 and attracts T cells for efficient antigen presentation. Our previous studies showed that FKN was up-regulated in the serum and renal glomerulus of patients with lupus nephritis. Moreover, CX3CR1 deficiency can protect inflammatory reaction through decreasing specific responses of Th17 cells. However, it is unclear that how FKN regulates the pathogenesis of SLE through activating Th17. In our project, we determined the effects of FKN on the differentiation, phenotype and function of Th17 cells in CD4+ T cells, derived from lupus mice, with overexpressing or depleting FKN using the CRISPR/Cas9 system technology. In the MRL/lpr, (NZB/W) F1 and Pristane-induced lupus mice, the regulatory effects and molecular mechanisms of FKN on the activation of Th17 cells in the pathogenesis of SLE were investigated by molecular biology, immunology and pathology methods. Furthermore, the effects of FKN depletion in lupus mice models on the cytokines and signaling pathways were explored as the potential treatments. Overall, our study could provide a rationale for targeting FKN in SLE as a novel and promising therapy.