Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Pediatrics, Yueyang Hospital of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Inflamm Bowel Dis. 2023 May 2;29(5):818-829. doi: 10.1093/ibd/izac199.
Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are characterized by chronic idiopathic inflammation of gastrointestinal tract. Although the pathogenesis of IBD remains unknown, intestinal immune dysfunction has been considered as the core pathogenesis. In the intestinal immune system, T helper 1 (Th1) and Th17 cells are indispensable for intestine homeostasis via preventing pathogenic bacteria invasion, regulating metabolism and functions of intestinal epithelial cells (IECs), and promoting IEC self-renewal. However, during the development of IBD, Th1 and Th17 cells acquire the pathogenicity and change from the maintainer of intestinal homeostasis to the destroyer of intestinal mucosa. Because of coexpressing interferon-γ and interleukin-17A, Th17 cells with pathogenicity are named as pathogenic Th17 cells. In disease states, Th1 cells impair IEC programs by inducing IEC apoptosis, recruiting immune cells, promoting adhesion molecules expression of IECs, and differentiating to epithelial cell adhesion molecule-specific interferon γ-positive Th1 cells. Pathogenic Th17 cells induce IEC injury by triggering IBD susceptibility genes expression of IECs and specifically killing IECs. In addition, Th1 and pathogenic Th17 cells could cooperate to induce colitis. The evidences from IBD patients and animal models demonstrate that synergistic action of Th1 and pathogenic Th17 cells occurs in the diseases development and aggravates the mucosal inflammation. In this review, we focused on Th1 and Th17 cell programs in homeostasis and intestine inflammation and specifically discussed the impact of Th1 and Th17 cell pathogenicity and their synergistic action on the onset and the development of IBD. We hoped to provide some clues for treating IBD.
炎症性肠病（IBD），包括溃疡性结肠炎和克罗恩病，其特征为胃肠道的慢性特发性炎症。尽管 IBD 的发病机制尚不清楚，但肠道免疫功能障碍已被认为是核心发病机制。在肠道免疫系统中，辅助性 T 细胞 1（Th1）和 Th17 细胞对于通过防止病原细菌入侵、调节肠道上皮细胞（IEC）的代谢和功能以及促进 IEC 自我更新来维持肠道内稳态是不可或缺的。然而，在 IBD 的发展过程中，Th1 和 Th17 细胞获得了致病性，并从维持肠道内稳态的细胞转变为破坏肠道黏膜的细胞。由于共表达干扰素-γ和白细胞介素-17A，具有致病性的 Th17 细胞被命名为致病性 Th17 细胞。在疾病状态下，Th1 细胞通过诱导 IEC 凋亡、招募免疫细胞、促进 IEC 黏附分子表达以及分化为上皮细胞黏附分子特异性干扰素-γ阳性 Th1 细胞，破坏 IEC 程序。致病性 Th17 细胞通过触发 IEC 中 IBD 易感性基因的表达并特异性杀伤 IEC 来诱导 IEC 损伤。此外，Th1 和致病性 Th17 细胞可以协同诱导结肠炎。来自 IBD 患者和动物模型的证据表明，Th1 和致病性 Th17 细胞在疾病发展和加重黏膜炎症中存在协同作用。在这篇综述中，我们重点关注了 Th1 和 Th17 细胞在稳态和肠道炎症中的程序，并专门讨论了 Th1 和 Th17 细胞的致病性及其协同作用对 IBD 发病和发展的影响。我们希望为治疗 IBD 提供一些线索。
