Zhao Di, Cai Chenwen, Zheng Qing, Jin Shuang, Song Dongjuan, Shen Jun, Ran Zhihua
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):237-244. doi: 10.1016/j.bbrc.2016.12.160. Epub 2016 Dec 27.
The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair.
Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way.
Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply.
Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury.
结肠上皮修复过程中管腔内微生物与固有免疫之间的相互作用已广为人知。与此同时，抗生素在溃疡性结肠炎发作期间被广泛使用。抗生素使用导致的管腔微生物群破坏对上皮修复的可能影响鲜有讨论。固有层中的固有淋巴细胞（ILC）可受肠道微生物调节，导致结肠IL-22/pSTAT3水平改变，这被认为是上皮损伤后组织修复中的一个重要分子轴。本研究旨在探讨抗生素是否会干扰ILC依赖的组织修复。
在预先用不同抗菌谱试剂处理的小鼠中建立葡聚糖硫酸钠（DSS）诱导的结肠炎。检测DSS停用后组织修复的形态学和分子标志物。还记录了ILC群体和功能状态。进一步关注抗生素治疗后树突状细胞的反应，据称其以IL-23依赖的方式调节结肠ILC3。
使用万古霉素导致实验性结肠炎后组织修复延迟。在这种情况下，发现结肠IL-22/pSTAT3轴和ILC3群体均减少。万古霉素治疗减少了上游IL-23和产生IL-23的树突状细胞群体。树突状细胞数量减少可能是由于趋化因子和集落刺激因子供应不足。
激活ILC3的树突状细胞成熟需要有对万古霉素敏感的微生物群，从而在组织愈合过程中维持结肠中足够的IL-22/pSTAT3水平。操纵结肠微生物群可能有助于在炎症和损伤后实现结肠黏膜愈合。
