IL-13 receptor α2 promotes epithelial cell regeneration from radiation-induced small intestinal injury in mice
IL-13 receptor α2 promotes epithelial cell regeneration from radiation-induced small intestinal injury in mice
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DOI：
10.1053/j.gastro.2006.04.022
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发表时间：
2006-07-01
期刊：
影响因子：
29.4
通讯作者：
Dohi, Taeko
中科院分区：
文献类型：
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作者：
Kawashima, Rei;Kawamura, Yuki I.;Dohi, Taeko
背景与目的：细胞因子白介素4(IL-4)和白介素13(IL-13)对多种细胞类型具有多向作用，对病理改变和组织重塑均有影响。本研究旨在阐明IL-13的高亲和力诱骗受体IL-13受体α2(IL-13Rα2)在胃肠道上皮细胞更新和修复中的作用。方法：比较野生型(WT)小鼠和IL-4R(-/-)基因缺陷小鼠经3GyX射线全身照射后粘膜损伤后的再生过程。然后用IL-13Rα2人免疫球蛋白(Ig)嵌合蛋白治疗小鼠。结果：WT小鼠照射后固有层NK细胞IL-13基因表达上调。随着照射后空肠上皮细胞分裂旺盛，IL-13Rα2在肌成纤维细胞和成纤维细胞中的表达显著增加。相反，IL-4R(-/-)小鼠的上皮细胞修复延迟，尽管IL-13上调，但并未显示IL-13Rα2的短暂上调。在WT和IL-4R(-/-)小鼠的原代培养的小肠中加入IL-13而不是IL-4可引起上皮细胞损伤。用IL-13Rα2-Ig治疗IL-4R(-/-)小鼠后，照射后上皮细胞分裂数量增加，组织修复能力增强。此外，IL-13Rα-Ig治疗增加了12-Gy射线照射后WT小鼠肠道再生上皮细胞的微集落数量。结论：IL-13Rα2是胃肠道上皮细胞再生的主要调节因子。
Background & Aims: The cytokines interleukin (IL)-4 and IL-13 have pleiotropic effects on a variety of cell types and impact both pathologic changes and tissue remodeling. The aim of this study was to clarify the roles of IL-13 receptor alpha 2 (IL-13R alpha 2), which is the high-affinity decoy receptor for IL-13, in gastrointestinal tract epithelial cell turnover and repair. Methods: We have compared the regenerative process following mucosal damage induced by whole-body 3-Gy X-ray irradiation of wild-type (WT) and IL-4 receptor of gene-deficient (IL-4R(-/-)) mice. Then we treated mice with IL-13R alpha 2 human immunoglobulin (Ig) chimeric protein. Results: Upregulation of mRNA levels for IL-13 in NK cells in the lamina propria was seen after irradiation of WT mice. Concomitant with vigorous epithelial cell division in the jejunum following irradiation, expression of the IL-13R alpha 2 dramatically increased in myofibroblasts and fibroblasts. In contrast, epithelial cell repair was delayed in IL-4R(-/-) mice, which did not show transient up-regulation of IL-13R alpha 2, although up-regulation of IL-13 was seen. Addition of IL-13 but not IL-4 to primary cultures of small intestine from both WT and IL-4R(-/-) mice induced epithelial cell damage. Treatment of IL-4R(-/-) mice with IL-13R alpha 2-Ig resulted in increased numbers of dividing epithelial cells and improved tissue repair after irradiation. Further, treatment with IL-13R alpha-Ig increased numbers of microcolonies of regenerating epithelial cells in the intestine of WT mice after severe damage induced by 12-Gy irradiation. Conclusions: The IL-13R alpha 2 is a major regulatory factor involved in the regeneration of epithelial cells in the gastrointestinal tract.