Nishina Takashi, Deguchi Yutaka, Kawauchi Mika, Xiyu Chen, Yamazaki Soh, Mikami Tetuo, Nakano Hiroyasu
Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan.
Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ota-ku, Tokyo 144-0032, Japan.
iScience. 2023 Jan 5;26(2):105934. doi: 10.1016/j.isci.2023.105934. eCollection 2023 Feb 17.
Intestinal homeostasis is tightly regulated by epithelial cells, leukocytes, and stromal cells, and its dysregulation is associated with inflammatory bowel diseases. Interleukin (IL)-11, a member of the IL-6 family of cytokines, is produced by inflammatory fibroblasts during acute colitis. However, the role of IL-11 in the development of colitis is still unclear. Herein, we showed that IL-11 ameliorated DSS-induced acute colitis in mouse models. We found that deletion of or rendered mice highly susceptible to DSS-induced colitis compared to the respective control mice. The number of apoptotic epithelial cells was increased in DSS-treated or deficient mice. Moreover, we showed that IL-11 production was regulated by reactive oxygen species (ROS) produced by -positive myeloid cells. These findings indicate that fibroblast-produced IL-11 plays an important role in protecting the mucosal epithelium in acute colitis. Myeloid cell-derived ROS contribute to the attenuation of colitis through the production of IL-11.
肠道稳态由上皮细胞、白细胞和基质细胞严格调控，其失调与炎症性肠病相关。白细胞介素（IL）-11是IL-6细胞因子家族的成员之一，在急性结肠炎期间由炎性成纤维细胞产生。然而，IL-11在结肠炎发展中的作用仍不清楚。在此，我们表明IL-11可改善小鼠模型中右旋糖酐硫酸钠（DSS）诱导的急性结肠炎。我们发现，与各自的对照小鼠相比，敲除或缺失IL-11使小鼠对DSS诱导的结肠炎高度敏感。在DSS处理的IL-11敲除或缺陷小鼠中，凋亡上皮细胞的数量增加。此外，我们表明IL-11的产生受CD11b阳性髓样细胞产生的活性氧（ROS）调节。这些发现表明，成纤维细胞产生的IL-11在急性结肠炎中保护黏膜上皮方面发挥重要作用。髓样细胞衍生的ROS通过产生IL-11促进结肠炎的减轻。
