Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens.
Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens.
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DOI：
10.4049/jimmunol.162.4.1884
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发表时间：
1999-02
影响因子：
4.4
通讯作者：
S. Wirtz;S. Finotto;S. Kanzler;A. Lohse;M. Blessing;H. Lehr;P. Galle;M. Neurath
中科院分区：
文献类型：
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作者：
S. Wirtz;S. Finotto;S. Kanzler;A. Lohse;M. Blessing;H. Lehr;P. Galle;M. Neurath
我们产生了STAT-4的转基因小鼠，STAT-4是一种在CMV启动子控制下与IL-12信号传导特异性相关的调节蛋白。这些小鼠在全身给予二硝基苯-钥孔血蓝蛋白后，固有层CD 4 + T淋巴细胞中的核STAT-4水平显著增加，并发展为以主要CD 4 + T淋巴细胞浸润为特征的慢性透壁性结肠炎。后一种细胞在用α CD 3/CD 28或自体细菌Ag活化后主要产生TNF和IFN-γ，但不产生IL-4，这与Th 1型细胞应答一致。此外，STAT-4转基因小鼠中的慢性结肠炎可以通过结肠和脾脏的CD 4 + T细胞过继转移到SCID小鼠，所述CD 4 + T细胞被来自自体细菌植物群的Ag激活。这些数据建立了涉及STAT-4的慢性肠道炎症发病机制的关键分子信号传导途径，并且该途径的靶向可能与人类结肠炎的治疗相关。
We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter. These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4+ T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4+ T lymphocytes. The latter cells produced predominantly TNF and IFN-gamma but not IL-4 upon activation with alphaCD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response. Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4+ T cells that were activated with Ags from autologous bacterial flora. These data establish a critical molecular signaling pathway involving STAT-4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway may be relevant for the treatment of colitis in humans.