TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells
TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells
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DOI：
10.1038/ni.2920
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发表时间：
2014-07-01
影响因子：
30.5
通讯作者：
Neurath, Markus F.
中科院分区：
文献类型：
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作者：
Gerlach, Katharina;Hwang, YouYi;Neurath, Markus F.
导致炎症性肠病的分子检查点还不完全清楚。在这里，我们发现在溃疡性结肠炎患者中有更多的T细胞表达转录因子PU1和白介素9(IL-9)。在一个动物模型中，在恶唑酮诱导的实验性结肠炎中，柠檬碱报告小鼠有更多的IL-9表达的粘膜T细胞。IL-9缺乏抑制了急、慢性结肠炎。T细胞PU.1缺乏的小鼠可以预防结肠炎，而IL-9抗体治疗可以抑制结肠炎。在体内，IL-9在功能上损害了肠屏障功能，阻止了粘膜伤口的愈合。因此，我们的研究结果表明，T(H)9辅助T细胞亚群通过调节肠上皮细胞在推动溃疡性结肠炎中发挥重要作用，T(H)9细胞可能是治疗慢性肠炎的靶点。
The molecular checkpoints that drive inflammatory bowel diseases are incompletely understood. Here we found more T cells expressing the transcription factor PU.1 and interleukin 9 (IL-9) in patients with ulcerative colitis. In an animal model, citrine reporter mice had more IL-9-expressing mucosal T cells in experimental oxazolone-induced colitis. IL-9 deficiency suppressed acute and chronic colitis. Mice with PU.1 deficiency in T cells were protected from colitis, whereas treatment with antibody to IL-9 suppressed colitis. Functionally, IL-9 impaired intestinal barrier function and prevented mucosal wound healing in vivo. Thus, our findings suggest that the T(H)9 subset of helper T cells serves an important role in driving ulcerative colitis by regulating intestinal epithelial cells and that T(H)9 cells represent a likely target for the treatment of chronic intestinal inflammation.