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The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model
Mucosal Immunology ( IF 8 ) Pub Date : 2019-01-07 , DOI: 10.1038/s41385-018-0123-3
J Sung 1 , C P Sodhi 2 , L Voltaggio 3 , X Hou 4 , H Jia 2 , Q Zhou 2 , D Čiháková 3 , D J Hackam 1, 2
Affiliation  

Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.



中文翻译:

在小鼠联体共生模型中,将肠外细胞募集到受损粘膜可促进放射性肠炎和化学性结肠炎的愈合

粘膜愈合是通过受损上皮内细胞的迁移和增殖而发生的,但在粘膜被剥脱的严重损伤后,这些过程可能不足以促进粘膜愈合。我们假设肠外细胞有助于小肠和大肠损伤后的粘膜愈合。我们在野生型和 tdTomato 小鼠之间生成了联体生物对,然后使它们遭受辐射诱导的肠炎和 2,4,6-三硝基苯磺酸 (TNBS) 诱导的结肠炎。我们现在表明,与单只小鼠相比,具有联生伴侣的小鼠可以免受肠道损伤,表现为体重减轻显着减少、促炎细胞因子表达减少、肠上皮细胞凋亡减少和隐窝增殖改善。供体细胞表达 CD45 -、Sca-1 +、c-kit +和 CXCR4 +,并在受伤的隐窝周围积聚,但没有转分化为上皮细胞,表明肠外细胞在愈合反应中发挥旁分泌作用,而共生配对使用 Rag1 -/- 的小鼠表现出更好的愈合效果,表明适应性免疫细胞对于粘膜愈合来说是可有可无的。引人注目的是,捐献者的骨髓消融消除了保护作用。这些发现表明,将肠外骨髓来源的细胞募集到受损的肠粘膜中可以促进粘膜愈合,这为严重肠道疾病提供了新的治疗方法。

更新日期:2019-05-16
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