先天性免疫系统中T-bet缺乏诱导的传染性溃疡性结肠炎。

Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.

作者信息

Garrett Wendy S, Lord Graham M, Punit Shivesh, Lugo-Villarino Geanncarlo, Mazmanian Sarkis K, Ito Susumu, Glickman Jonathan N, Glimcher Laurie H

机构信息

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

出版信息

Cell. 2007 Oct 5;131(1):33-45. doi: 10.1016/j.cell.2007.08.017.

Abstract

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.

摘要

炎症性肠病(IBD)被认为归因于宿主免疫反应过度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性免疫中协调炎症基因程序。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一个深刻且意想不到的功能。先天性免疫系统中T-bet的缺乏会导致在没有适应性免疫的情况下出现自发性且具有传染性的溃疡性结肠炎,并且在免疫功能正常的宿主中增加患结肠炎的易感性。T-bet通过调节结肠树突状细胞中肿瘤坏死因子-α(TNF-α)的产生来控制黏膜免疫系统对共生细菌的反应,这对维持结肠上皮屏障至关重要。T-bet的缺失会影响细菌群体,使其具有致结肠炎的特性,并且这种结肠炎可传染给基因完整的宿主。这些发现揭示了T-bet作为宿主与共生关系调节者的新功能,并为IBD的病理生理学提供了新的视角。

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