介素-22促进肠干细胞介导的上皮再生
Caroline A Lindemans1,2, Marco Calafiore1, Anna M Mertelsmann1
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Nature
|December 10, 2015
概括
在受伤后,先天性淋巴细胞 (ILC) 通过产生INTERLEUKIN-22 (IL-22) 来促进肠上皮的再生. 直接激活肠道干细胞 (ISC),促进它们的生长和帮助组织修复.
科学领域:
- 免疫学
- 胃肠病学
- 干细胞生物学
背景情况:
- 肠上皮的再生对于受伤后的器官功能至关重要.
- 肠干细胞 (ISC) 通过特定的信号通路来调节正常的上皮细胞维护.
- 肠道损伤后的ISC区的调节仍然不完全理解.
研究的目的:
- 研究先天性淋巴细胞 (ILC) 和IL-22在肠上皮再生中的作用.
- 阐明IL-22影响肠干细胞 (ISC) 并促进组织修复的机制.
主要方法:
- 使用ex vivo肠道器官培养物 (老鼠和人类) 来评估生长.
- 对有机体和体内模型进行了重组IL-22.
- 分析了STAT3酸化和ATOH1缺乏与IL-22的影响相关.
- 在体内研究涉及异性骨髓移植模型.
主要成果:
- 从ILC衍生的IL-22显著增加了小鼠小肠器官的成长,这种成长方式依赖于IL-22.
- 在小鼠和人类器官中,重组IL-22直接促进了ISC的增殖和扩张.
- IL-22在Lgr5(+) ISC中诱导了STAT3酸化,这对于有机体的形成和再生至关重要.
- 在活体IL-22治疗改善了ISC恢复,上皮再生,并减少了移植对宿主疾病模型.
结论:
- 由先天性淋巴细胞 (ILCs) 产生的介素-22 (IL-22) 是支持肠道上皮再生的关键免疫媒介.
- 通过STAT3信号,IL-22直接激活肠道干细胞 (ISC),促进独立于Paneth细胞的增殖和修复.
- 这项研究揭示了一条关键的免疫-干细胞通讯途径,
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