T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T...T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.展开更多
为检测Asia1口蹄疫（Foot and mouth disease，FMD）重组病毒免疫原性和安全性，将构建表达Asia1型口蹄疫病毒（Foot and mouth disease virus，FMDV）3C基因、P1—2A基因和猪白细胞介素18（Interleukin 18，IL-18）基因的重组鸡痘病毒r...为检测Asia1口蹄疫（Foot and mouth disease，FMD）重组病毒免疫原性和安全性，将构建表达Asia1型口蹄疫病毒（Foot and mouth disease virus，FMDV）3C基因、P1—2A基因和猪白细胞介素18（Interleukin 18，IL-18）基因的重组鸡痘病毒rFPV-P1—2A-3C和rFPV-3C—P1—2A-IL-18间隔2周免疫豚鼠3次，进行特异性抗体、中和抗体、淋巴细胞增殖、淋巴细胞亚类数量、IFN—γ、攻毒保护以及体内分布研究。重组鸡痘病毒可有效刺激豚鼠产生特异性抗体、中和抗体、T淋巴细胞亚类数量、IFN-γ分泌均显著高于对照组；重组鸡疽病毒rFPV-3C-P1—2A—IL-18的T淋巴细胞亚类数量、T淋巴细胞转化和IFN-γ分泌高于重组病毒rFPV-P1—2A-3C免疫组；2个重组病毒的攻毒保护率分别为4／5、3／5。2个重组病毒在接种最早12h可检测到重组病毒的基因，最晚7d可检测到重组病毒的基因。结果表明重组鸡痘病毒rFPV—P1—2A-3C和rFPV-3C-P1—2A—IL-18具有良好的免疫原性，可以有效抵御病毒的攻击，体内残留时间短，对免疫动物安全，为开发、应用新型FMDV疫苗奠定了基础。展开更多
基金the National Natural Science Foundation of China(81430033,81871269,91942311 and 31930035)。
文摘T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.
文摘为检测Asia1口蹄疫（Foot and mouth disease，FMD）重组病毒免疫原性和安全性，将构建表达Asia1型口蹄疫病毒（Foot and mouth disease virus，FMDV）3C基因、P1—2A基因和猪白细胞介素18（Interleukin 18，IL-18）基因的重组鸡痘病毒rFPV-P1—2A-3C和rFPV-3C—P1—2A-IL-18间隔2周免疫豚鼠3次，进行特异性抗体、中和抗体、淋巴细胞增殖、淋巴细胞亚类数量、IFN—γ、攻毒保护以及体内分布研究。重组鸡痘病毒可有效刺激豚鼠产生特异性抗体、中和抗体、T淋巴细胞亚类数量、IFN-γ分泌均显著高于对照组；重组鸡疽病毒rFPV-3C-P1—2A—IL-18的T淋巴细胞亚类数量、T淋巴细胞转化和IFN-γ分泌高于重组病毒rFPV-P1—2A-3C免疫组；2个重组病毒的攻毒保护率分别为4／5、3／5。2个重组病毒在接种最早12h可检测到重组病毒的基因，最晚7d可检测到重组病毒的基因。结果表明重组鸡痘病毒rFPV—P1—2A-3C和rFPV-3C-P1—2A—IL-18具有良好的免疫原性，可以有效抵御病毒的攻击，体内残留时间短，对免疫动物安全，为开发、应用新型FMDV疫苗奠定了基础。
