Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143, USA.
Sci Transl Med. 2010 Dec 1;2(60):60ra88. doi: 10.1126/scitranslmed.3001500.
Ulcerative colitis, a type of inflammatory bowel disease, is less common in countries endemic for helminth infections, suggesting that helminth colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases. Indeed, therapeutic effects of experimental helminth infection have been reported in both animal models and clinical trials. Here, we provide a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Tissue with active colitis had a prominent population of mucosal T helper (T(H)) cells that produced the inflammatory cytokine interleukin-17 (IL-17) but not IL-22, a cytokine involved in mucosal healing. After helminth exposure, the disease went into remission, and IL-22-producing T(H) cells accumulated in the mucosa. Genes involved in carbohydrate and lipid metabolism were up-regulated in helminth-colonized tissue, whereas tissues with active colitis showed up-regulation of proinflammatory genes such as IL-17, IL-13RA2, and CHI3L1. Therefore, T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through T(H)2 cytokines and IL-22. Improved understanding of the physiological effects of helminth infection may lead to new therapies for inflammatory bowel diseases.
溃疡性结肠炎是一种炎症性肠病,在寄生虫感染流行的国家较少见,这表明寄生虫定植可能具有调节炎症性肠病肠道炎症的潜力。事实上,实验性寄生虫感染的治疗效果已在动物模型和临床试验中得到报道。在这里,我们提供了一个个体感染 Trichuris trichiura 治疗溃疡性结肠炎症状的肠道黏膜中动态变化的全面细胞和分子特征。活动性结肠炎的组织中存在大量黏膜辅助性 T 细胞 (T(H)),这些细胞产生炎症细胞因子白细胞介素-17 (IL-17),但不产生参与黏膜愈合的细胞因子白细胞介素-22。在寄生虫暴露后,疾病缓解,IL-22 产生的 T(H)细胞在黏膜中积累。碳水化合物和脂质代谢相关基因在寄生虫定植组织中上调,而活动性结肠炎组织中则上调促炎基因,如白细胞介素-17、白细胞介素-13RA2 和 CHI3L1。因此,肠道中的 T. trichiura 定植可能通过 T(H)2 细胞因子和 IL-22 促进杯状细胞增生和黏液产生,从而减轻症状性结肠炎。对寄生虫感染生理作用的深入了解可能为炎症性肠病提供新的治疗方法。