Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system
Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system
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DOI：
10.1016/j.cell.2007.08.017
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发表时间：
2007-10-05
期刊：
影响因子：
64.5
通讯作者：
Glimcher, Laurie H.
中科院分区：
文献类型：
--
作者：
Garrett, Wendy S.;Lord, Graham M.;Glimcher, Laurie H.
炎症性肠病（IBD）归因于宿主免疫力过度旺盛或有害肠道菌群的出现。转录因子 T-bet 在适应性免疫和先天免疫中协调炎症遗传程序。我们描述了 T-bet 在影响宿主炎症活动和共生细菌行为方面的深远且意想不到的功能。先天免疫系统中的 T-bet 缺陷会在缺乏适应性免疫的情况下导致自发性和传染性溃疡性结肠炎，并增加免疫完整宿主对结肠炎的易感性。 T-bet 通过调节结肠树突细胞中 TNF-α 的产生来控制粘膜免疫系统对共生细菌的反应，这对于结肠上皮屏障的维持至关重要。 T-bet 的缺失会影响细菌群产生结肠炎，而这种结肠炎可以传染给基因完整的宿主。这些发现揭示了 T-bet 作为宿主共生关系的维和者的新功能，并为 IBD 的病理生理学提供了新的视角。
Inflammatory bowel disease (IBD) has been attributed to overexuberant host immunity or the emergence of harmful intestinal flora. The transcription factor T-bet orchestrates inflammatory genetic programs in both adaptive and innate immunity. We describe a profound and unexpected function for T-bet in influencing the behavior of host inflammatory activity and commensal bacteria. T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence of adaptive immunity and increased susceptibility to colitis in immunologically intact hosts. T-bet controls the response of the mucosal immune system to commensal bacteria by regulating TNF-alpha production in colonic dendritic cells, critical for colonic epithelial barrier maintenance. Loss of T-bet influences bacterial populations to become colitogenic, and this colitis is communicable to genetically intact hosts. These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD.