滤泡辅助性T（Tfh）细胞是一群专职辅助B细胞免疫的新型CD4+T细胞亚群，其数量和功能异常可导致系统性红斑狼疮（SLE）的发生。最新研究发现，Toll样受体7（TLR7）能负向调控CD4+T细胞的功能，但TLR7能否负向调控Tfh细胞在SLE中的作用及其机制尚不清楚。为此，本研究拟通过流式细胞术、免疫荧光显微术、Real-time PCR、Western blot等方法，在小鼠体内外观察TLR7激动剂Imiquimod（IMQ）对Tfh细胞增殖分化及其辅助B细胞免疫的影响，明确TLR7对Tfh细胞的负向调控作用；通过观察IMQ对Tfh细胞分化相关的转录因子Bcl-6、STAT3、NFAT、IRF4等mRNA及蛋白表达的影响，探讨TLR7调节Tfh细胞的分子机制；最后，以SLE模型小鼠为研究对象，阐明TLR7激动剂负向调控Tfh细胞在SLE中的作用及机制，为SLE的治疗提供新思路和新靶点。

Follicular helper T cells (Tfh cells), a novel subset of CD4+T cells are specialized in helping B cells. It leads to the autoimmune diseases such as Systemic Lupus Erythematosus (SLE) when its numbers and functions are been mis-conducted. Recently, a new study has been found that Toll Like Receptor 7 (TLR7) can negatively regulate the function of CD4 + T cells. So far, there is not clear whether TLR7 can negatively regulate the function of Tfh cells in SLE and the relative molecular mechanisms. Therefore, this project plans to investigate the proliferation and differentiation of Tfh cells and its effect on helping B cells to produce antibodies from Mice in vivo and in vitro study by Flow Cytometry, Immunofluorescence technique, Real-time PCR，Western blot and so on, to identify the function of the regulating Tfh cells immune response through Ligand, Imiquimod(IMQ) activation. Furthermore, in order to explore the molecular mechanism of regulating Tfh cells by TLR7, it plans to evaluate the expression of mRNA and protein of the transcriptional factor of Bcl-6、STAT3、NFAT、IRF4 and so on during the differentiation of Tfh cells to IMQ activating response. Finally, we will establish the SLE mice model for the study, to explore the mechanism of negatively regulating Tfh cells by TLR7 in SLE mice model, providing the new ideas and new targets for treating SLE.