Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2010, Cincinnati, OH, 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sci Rep. 2021 May 5;11(1):9575. doi: 10.1038/s41598-021-89119-1.
IL-33 is upregulated in ulcerative colitis and has a protective role in chemically-induced acute murine colitis. We aimed to determine whether IL-33 influences Il10 chronic colitis and its cellular source in health and during colitis. Il10Il33 and Il10Il33 littermates developed colitis of similar severity. Colon Il33 was induced in WT and Il10 mice exposed to DSS, but not in unchallenged Il10 mice with colitis. Il33-citrine reporter mice showed that Il33-citrine colocalized with α-smooth muscle actin myofibroblasts and vimentin fibroblasts in WT mice. CitrineCD74CD90 inflammatory fibroblasts were increased with DSS treatment. IL-1β induced Il33 expression in colon myofibroblasts, but colon Il33 expression did not differ between DSS-treated WT and Il1r1 mice. In conclusion, deficiency of IL-33 does not alter the severity of chronic colitis in Il10 mice. Induction of Il33 upon DSS exposure in WT and Il10 mice, but not in unchallenged Il10 mice, suggests epithelial injury induces colon IL-33. Fibroblasts are the primary colonic source of IL-33 and IL-33-expressing CD90CD74 fibroblasts are increased during DSS-induced colitis. IL-1β induces Il33 in colon myofibroblasts in vitro, but signaling through the IL-1R1 is not necessary for induction of IL-33 in DSS-induced colitis.
IL-33 在溃疡性结肠炎中上调，并在化学诱导的急性小鼠结肠炎中具有保护作用。我们旨在确定 IL-33 是否影响健康和结肠炎期间的 Il10 慢性结肠炎及其细胞来源。Il10Il33 和 Il10Il33 同窝仔在接受 DSS 处理后发展出相似严重程度的结肠炎，但在没有结肠炎的 Il10 小鼠中未诱导出结肠 Il33。在暴露于 DSS 的 WT 和 Il10 小鼠中诱导了 Il33-citrine 报告基因，但在未受挑战的具有结肠炎的 Il10 小鼠中未诱导。Il33-citrine 报告基因小鼠显示 Il33-citrine 与 WT 小鼠中的α-平滑肌肌动蛋白肌成纤维细胞和波形蛋白成纤维细胞共定位。CitrineCD74CD90 炎性成纤维细胞在 DSS 处理时增加。IL-1β 在结肠肌成纤维细胞中诱导 Il33 表达，但在 DSS 处理的 WT 和 Il1r1 小鼠之间，结肠 Il33 表达没有差异。总之，IL-33 缺乏不会改变 Il10 小鼠慢性结肠炎的严重程度。在 WT 和 Il10 小鼠中，在暴露于 DSS 时诱导 Il33，但在未受挑战的 Il10 小鼠中未诱导，这表明上皮损伤诱导结肠 IL-33。成纤维细胞是结肠中 IL-33 的主要来源，并且在 DSS 诱导的结肠炎期间，表达 IL-33 的 CD90CD74 成纤维细胞增加。IL-1β 在体外诱导结肠肌成纤维细胞中的 Il33，但在 DSS 诱导的结肠炎中，IL-1R1 信号传导不是诱导 IL-33 所必需的。
