Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration.
Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration.
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DOI：
10.1016/j.xcrm.2021.100320
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发表时间：
2021-06-15
期刊：
影响因子：
--
通讯作者：
Good M
中科院分区：
文献类型：
--
作者：
Mihi B;Gong Q;Nolan LS;Gale SE;Goree M;Hu E;Lanik WE;Rimer JM;Liu V;Parks OB;Lewis AN;Agrawal P;Laury ML;Kumar P;Huang E;Bidani SS;Luke CJ;Kolls JK;Good M
坏死性小肠结肠炎（NEC）是一种致命的肠道炎症性疾病，主要影响早产儿，缺乏足够的治疗。白细胞介素（IL）-22在成年动物模型中在肠道屏障维持、促进上皮再生和控制肠道炎症中起关键作用。然而，IL-22信号在NEC期间新生儿中的重要性仍然未知。我们研究了IL-22在新生儿肠道稳态和炎症条件下使用NEC小鼠模型的作用。我们的数据表明，在断奶之前，新生鼠肠道中IL-22的表达可以忽略不计，并且人和鼠新生儿在NEC期间都缺乏IL-22的产生。缺乏IL-22或肠道中缺乏IL-22受体的小鼠显示出对NEC的相似易感性，这与发育期间缺乏内源性IL-22一致。引人注目的是，在NEC期间用重组IL-22治疗显著减少炎症并增强上皮再生。这些发现可能为减轻NEC提供新的治疗策略。肠早产的特征在于缺乏有效的IL-22产生rIL-22增强NEC期间肠上皮的再生和完整性rIL-22驱动的抗菌反应不影响新生儿微生物组组成坏死性小肠结肠炎（NEC）是一种治疗选择有限的致命肠道疾病。白细胞介素（IL）-22在胃肠疾病的成年动物模型中控制肠道炎症中起作用。Mihi等人证明IL-22可以通过促进NEC新生小鼠模型中的上皮再生来减轻肠道炎症。
Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC. Intestinal prematurity is characterized by the lack of efficient IL-22 production rIL-22 enhances the regeneration and integrity of intestinal epithelium during NEC rIL-22-driven antimicrobial response does not affect neonatal microbiome composition Necrotizing enterocolitis (NEC) is a deadly intestinal disease with limited treatment options. Interleukin (IL)-22 plays a role in controlling intestinal inflammation in adult animal models of gastrointestinal disease. Mihi et al. demonstrate that IL-22 can attenuate intestinal inflammation by promoting epithelial regeneration in a neonatal mouse model of NEC.
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