Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
MRC Laboratory of Molecular Biology, Cambridge, UK.
Nat Immunol. 2014 Jul;15(7):676-86. doi: 10.1038/ni.2920. Epub 2014 Jun 8.
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 TH9 subset of helper T cells serves an important role in driving ulcerative colitis by regulating intestinal epithelial cells and that TH9 cells represent a likely target for the treatment of chronic intestinal inflammation.
驱动炎症性肠病的分子检查点尚不完全清楚。在这里，我们发现溃疡性结肠炎患者中有更多表达转录因子 PU.1 和白细胞介素 9 (IL-9) 的 T 细胞。在动物模型中，Citrine 报告小鼠在实验性 oxazolone 诱导的结肠炎中具有更多表达 IL-9 的粘膜 T 细胞。IL-9 缺乏可抑制急性和慢性结肠炎。T 细胞中缺乏 PU.1 的小鼠可免受结肠炎的影响，而抗 IL-9 抗体的治疗可抑制结肠炎。功能上，IL-9 损害肠道屏障功能并防止体内粘膜伤口愈合。因此，我们的研究结果表明，辅助性 T 细胞的 TH9 亚群通过调节肠道上皮细胞在溃疡性结肠炎的发病中起重要作用，并且 TH9 细胞可能是治疗慢性肠道炎症的潜在靶点。
