T-bet knockout prevents Helicobacter felis-induced gastric cancer.
T-bet knockout prevents Helicobacter felis-induced gastric cancer.
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DOI：
10.4049/jimmunol.0900511
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Houghton J
中科院分区：
文献类型：
--
作者：
Stoicov C;Fan X;Liu JH;Bowen G;Whary M;Kurt-Jones E;Houghton J
幽门螺杆菌感染是胃癌的主要危险因素，胃粘膜内的细胞因子环境是疾病风险的最强预测因子。升高的TNF-α、IL-1β和低的IL-10与最高的风险相关。在这项研究中，我们使用C57BL/6小鼠来鉴定T-bet是猫幽门螺杆菌感染期间细胞因子环境的中心调节因子。在不同的时间点，我们用雄性和雌性C57BL/6和C57BL/6- t -bet敲除（KO）的雄、雌交配体感染猫狸，并检测细菌定植、免疫反应和粘膜损伤。T-bet KO小鼠与野生型小鼠保持了15个月的感染水平。感染和免疫反应在雄性和雌性小鼠之间没有差异。尽管持续感染，T-bet KO小鼠对Th1反应迟钝，这与保存壁细胞和主细胞以及防止胃癌发展有关。出乎意料的是，T-bet KO小鼠形成了一种单独基于T-bet KO CD4细胞表型的胃部环境。T-bet KO小鼠对H. felis感染的反应是IL-1β和TNF-α明显减弱，IL-10水平升高。这一主调控因子的活性调节与胃癌相关的关键胃黏膜细胞因子的表达，可能是临床治疗胃癌高危患者恢复免疫平衡的靶点。
Helicobacter infection is the primary risk factor for gastric cancer, with the cytokine environment within the gastric mucosa the strongest predictor of disease risk. Elevated TNF-α, IL-1β, and low IL-10 are associated with the highest risk. In this study, we used C57BL/6 mice to identify T-bet as a central regulator of the cytokine environment during Helicobacter felis infection. We infected male and female C57BL/6 and C57BL/6-T-bet knockout (KO) liter mates with H. felis and examined the bacterial colonization, immune response, and mucosal damage at varying time points. T-bet KO mice maintained infection for 15 mo at similar levels to wild-type mice. Infection and immune response did not differ between male and female mice. Despite sustained infection, T-bet KO mice respond with a blunted Th1 response associated with preservation of parietal and chief cells and protection from the development of gastric cancer. Unexpectedly, T-bet KO mice develop a gastric environment that would not be expected based on the phenotype of T-bet KO CD4 cells alone. T-bet KO mice respond to H. felis infection with a markedly blunted IL-1β and TNF-α and elevated IL-10 levels. Activity of this one master regulator modulates the expression of the key gastric mucosal cytokines associated with gastric cancer and may be a target for therapy to restore immune balance clinically in patients at risk for gastric cancer.
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影响因子：
4.2
作者：
Peek RM
通讯作者：
Peek RM
DOI：
10.1073/pnas.0700021104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Aliprantis, Antonios O.;Wang, Jingsong;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.
影响因子：
82.9
作者：
Fox, JG;Beck, P;Nagler-Anderson, C
通讯作者：
Nagler-Anderson, C
影响因子：
254.7
作者：
Landis, SH;Murray, T;Wingo, PA
通讯作者：
Wingo, PA
DOI：
10.1084/jem.20011956
发表时间：
2002-05-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Neurath MF;Weigmann B;Finotto S;Glickman J;Nieuwenhuis E;Iijima H;Mizoguchi A;Mizoguchi E;Mudter J;Galle PR;Bhan A;Autschbach F;Sullivan BM;Szabo SJ;Glimcher LH;Blumberg RS
通讯作者：
Blumberg RS