Interleukin-21(IL-21)is produced mainly by activated CD4^(+)T cells and promotes the proliferation,survival and differentiation of immune cells.This study characterised a high affinity binding receptor of IL-21(IL-21 ...Interleukin-21(IL-21)is produced mainly by activated CD4^(+)T cells and promotes the proliferation,survival and differentiation of immune cells.This study characterised a high affinity binding receptor of IL-21(IL-21 Rα)from grass carp(Ctenopharyngodon idella,Ci)and analyzed the expression of CiIL-21 and CiIL-21 Rα.It has been shown that they were modulated by PAMPs and during infection with bacterial and viral pathogens.Recombinant CiIL-21 protein produced in bacteria was active in inducing the expression of genes involved in Th responses.A monoclonal CiIL-21 antibody was generated against the rCiIL-21 and showed good reactive specificity with the rCiIL-21 proteins expressed in E.coli cells,and HEK293 T cells and the native protein from PHA-stimulated kidney leukocytes.In addition,the IL-21-producing cells detected by the CiIL-21 monoclonal antibody were found to be increased to in the kidney,spleen and hindgut after infection with Flavobacterium columnare.Our data indicate that IL-21 is involved in the regulation of immune response to bacterial and viral infection.展开更多
目的检测白细胞介素21(interleukin-21,IL-21)、白细胞介素21受体(interleukin-21 recepter,IL-21R)及信号传导和转录激活因子3(signal transducers and activators of transcription 3,STAT3)在实验性自身免疫性肝炎(experimental auto...目的检测白细胞介素21(interleukin-21,IL-21)、白细胞介素21受体(interleukin-21 recepter,IL-21R)及信号传导和转录激活因子3(signal transducers and activators of transcription 3,STAT3)在实验性自身免疫性肝炎(experimental autoimmune hepatitis,EAH)模型小鼠肝损伤中的表达情况,探讨IL-21/STAT3通路在其发病中的作用和机理。方法建立EAH,于造模后第4周发病高峰期取材,检测各组小鼠血清生化水平并观察肝脏组织病理改变;酶联免疫吸附试验(ELISA法)测定血清中IL-21和IL-6的表达水平,并行IL-21与IL-6、IL-21、ALT相关性分析;流式细胞技术检测IL-21R在肝脏T淋巴细胞上表达情况;实时荧光定量PCR技术检测肝组织中IL-21和STAT3的基因转录表达水平;免疫组化方法检测肝组织中IL-21和STAT3的蛋白表达。结果模型建立后第4周,模型组血清ALT、AST水平与正常对照组相比明显升高;血清IL-21、IL-6含量明显增加并具有相关性;血清IL-21水平与ALT水平呈正相关;肝组织中有明显的炎症细胞浸润聚集,肝脏CD4^+T及CD8^+T细胞上IL-21R表达水平上调,以CD4^+T为著;肝组织IL-21和STAT3 mRNA及蛋白水平均明显升高。结论在炎症微环境中,IL-21表达水平升高且其受体表达水平上调,IL-21/STAT3通路被激活,从而促进自身免疫性肝损伤,干预或阻断该通路有望成为治疗靶点和方法。展开更多
基金funded by the National Natural Science Foundation of China(Grant number:32030112)National Key R&D Program of China(Grant number:2018YFD0900302).
文摘Interleukin-21(IL-21)is produced mainly by activated CD4^(+)T cells and promotes the proliferation,survival and differentiation of immune cells.This study characterised a high affinity binding receptor of IL-21(IL-21 Rα)from grass carp(Ctenopharyngodon idella,Ci)and analyzed the expression of CiIL-21 and CiIL-21 Rα.It has been shown that they were modulated by PAMPs and during infection with bacterial and viral pathogens.Recombinant CiIL-21 protein produced in bacteria was active in inducing the expression of genes involved in Th responses.A monoclonal CiIL-21 antibody was generated against the rCiIL-21 and showed good reactive specificity with the rCiIL-21 proteins expressed in E.coli cells,and HEK293 T cells and the native protein from PHA-stimulated kidney leukocytes.In addition,the IL-21-producing cells detected by the CiIL-21 monoclonal antibody were found to be increased to in the kidney,spleen and hindgut after infection with Flavobacterium columnare.Our data indicate that IL-21 is involved in the regulation of immune response to bacterial and viral infection.
