Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Cell Transplant. 2023 Jan-Dec;32:9636897231177377. doi: 10.1177/09636897231177377.
Epithelial regeneration is critical for barrier maintenance and organ function after intestinal radiation injury. Accumulating evidence indicates that the interleukin family members play critical roles in intestinal stem-cell-mediated epithelial regeneration. However, little is known about the relationship between interleukin 33 (IL-33)/ST2 axis and intestinal regeneration after radiation injury. We demonstrate here that IL-33 expression significantly increased after radiation treatment. Deficiency of IL-33/ST2 promotes intestinal epithelial regeneration, resulting in a reduction of mortality during radiation-induced intestine injury. Using organoid cultures, we show that recombinant IL-33 promotes intestinal stem cell differentiation. Mechanistically, the effects of IL-33 were mediated by activation of transforming growth factor-β signaling. Our findings reveal a fundamental mechanism by which IL-33 is able to regulate the intestinal crypt regeneration after tissue damage.
上皮细胞再生对于肠道辐射损伤后的屏障维持和器官功能至关重要。越来越多的证据表明，白细胞介素家族成员在肠道干细胞介导的上皮再生中发挥着关键作用。然而，关于白细胞介素 33（IL-33）/ST2 轴与辐射损伤后肠道再生之间的关系知之甚少。我们在这里证明，IL-33 表达在辐射处理后显著增加。IL-33/ST2 的缺失促进了肠道上皮细胞的再生，从而降低了辐射诱导的肠道损伤期间的死亡率。通过类器官培养，我们表明重组 IL-33 促进了肠道干细胞的分化。从机制上讲，IL-33 的作用是通过转化生长因子-β信号的激活来介导的。我们的研究结果揭示了 IL-33 能够调节组织损伤后肠道隐窝再生的基本机制。
