Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into ...Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into liver.Methods:Peripheral blood and liver tissue from 30 LC patients and 18 normal controls were recruited.The frequency of Th9 cells and CCR4,CCR6 in the peripheral blood was tested by flow cytometry.Serum interleukin(IL)-9 and CCL20 levels were tested by enzyme-linked immunosorbent assay.Immunohistochemical staining was used to detect a-smooth muscle actin,CCR6 and CCL20 expression in liver tissue.Results:The frequency of Th9 cells in LC patients was significantly increased compared with controls(P < 0.05).The serum IL-9 level and CCL20 level increased markedly in LC patients compared with controls(P < 0.05),and IL-9 was positively correlated to Th9 cells and CCL20.Furthermore,the frequency of Th9 cells was correlated to prothrombin time,total bilirubin level,hyaluronic acid and type IV collagen in LC patients.We also found that Th9 cells in LC patients expressed higher frequency of CCR4+,CCR6+(P < 0.05).Compared with normal controls,the expression of CCR6 and CCL20 in LC tissue were significantly elevated(P < 0.05).The expression of a-smooth muscle actin was correlated to the CCR6 and CCL20 in liver tissue of LC patients.Conclusions:This study suggests that Th9 cells may participate in the pathogenesis of LC,and the recruitment of Th9 cells into liver tissue might be through CCL20/CCR6 axis.展开更多
Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantia...Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.展开更多
辅助性T细胞(helper T cell,Th)9细胞是近年新发现的一种CD4+T细胞亚群,特异性分泌白细胞介素9(IL-9)。Th9细胞的诱导分化受到多种细胞因子与转录因子的影响,且与其他T细胞亚群间存在相互影响。IL-4和转化生长因子β是诱导其分化的关键...辅助性T细胞(helper T cell,Th)9细胞是近年新发现的一种CD4+T细胞亚群,特异性分泌白细胞介素9(IL-9)。Th9细胞的诱导分化受到多种细胞因子与转录因子的影响,且与其他T细胞亚群间存在相互影响。IL-4和转化生长因子β是诱导其分化的关键细胞因子,PU.1和干扰素调节因子4为调节其分化的重要转录因子。Th9细胞在炎症性疾病与肿瘤的发生、发展中发挥着重要作用,其生物学效应具有双向性,研究Th9细胞的分化发育及其在相关疾病中的具体作用,将为疾病的诊断治疗等提供新的线索。展开更多
基金Supported by grants from the National Natural Science Foundation of China(81260083,31360221)Natural Science Foundation of Guangxi Province(2014GXNSFAA118203)
文摘Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into liver.Methods:Peripheral blood and liver tissue from 30 LC patients and 18 normal controls were recruited.The frequency of Th9 cells and CCR4,CCR6 in the peripheral blood was tested by flow cytometry.Serum interleukin(IL)-9 and CCL20 levels were tested by enzyme-linked immunosorbent assay.Immunohistochemical staining was used to detect a-smooth muscle actin,CCR6 and CCL20 expression in liver tissue.Results:The frequency of Th9 cells in LC patients was significantly increased compared with controls(P < 0.05).The serum IL-9 level and CCL20 level increased markedly in LC patients compared with controls(P < 0.05),and IL-9 was positively correlated to Th9 cells and CCL20.Furthermore,the frequency of Th9 cells was correlated to prothrombin time,total bilirubin level,hyaluronic acid and type IV collagen in LC patients.We also found that Th9 cells in LC patients expressed higher frequency of CCR4+,CCR6+(P < 0.05).Compared with normal controls,the expression of CCR6 and CCL20 in LC tissue were significantly elevated(P < 0.05).The expression of a-smooth muscle actin was correlated to the CCR6 and CCL20 in liver tissue of LC patients.Conclusions:This study suggests that Th9 cells may participate in the pathogenesis of LC,and the recruitment of Th9 cells into liver tissue might be through CCL20/CCR6 axis.
基金This work was supported by National Natural Science Foundation of China(81872173,82072959,31870959,and 82102855)Zhejiang Province Natural Science Foundation(LY20H160018,LD21H160002,and LY19H160045).
文摘Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.
文摘辅助性T细胞(helper T cell,Th)9细胞是近年新发现的一种CD4+T细胞亚群,特异性分泌白细胞介素9(IL-9)。Th9细胞的诱导分化受到多种细胞因子与转录因子的影响,且与其他T细胞亚群间存在相互影响。IL-4和转化生长因子β是诱导其分化的关键细胞因子,PU.1和干扰素调节因子4为调节其分化的重要转录因子。Th9细胞在炎症性疾病与肿瘤的发生、发展中发挥着重要作用,其生物学效应具有双向性,研究Th9细胞的分化发育及其在相关疾病中的具体作用,将为疾病的诊断治疗等提供新的线索。
