Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism
Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism
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来自间充质基质细胞的外泌体通过巨噬细胞依赖性机制减少小鼠结肠炎症。
DOI：
10.1172/jci.insight.131273
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发表时间：
2019-12-19
期刊：
影响因子：
8
通讯作者：
Lan, Ping
中科院分区：
文献类型：
--
作者：
Liu, Huashan;Liang, Zhenxing;Lan, Ping
炎症性肠病（IBD）的常规治疗有多种潜在的副作用。因此，迫切需要替代治疗。这项工作表明，全身给予来自人骨髓源性间充质基质细胞（MSC-Exos）的外泌体显著减轻了各种IBD模型中的结肠炎。MSC-Exos治疗下调炎症反应，维持肠屏障完整性和极化M2 b巨噬细胞，但不利于肠纤维化。从机制上讲，输注的MSC-Exos主要作用于结肠巨噬细胞，并且当从用MSC-Exos处理的小鼠与未处理的小鼠制备时，来自结肠炎结肠的巨噬细胞获得对炎症再刺激的明显抗性。MSC-Exos的有益作用被巨噬细胞耗竭阻断。此外，诱导巨噬细胞产生IL-10部分参与了MSC-Exos的有益作用。MSC-Exos富含参与调节与MSC-Exos抗结肠炎益处相关的多种生物过程的蛋白质。特别是，MSC-Exos中的金属硫蛋白-2是抑制炎症反应所必需的。总之，MSC-Exos是炎症反应的关键调节剂，可能是IBD治疗的有希望的候选者。
Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. This work demonstrated that systemic administration of exosomes from human bone marrow-derived mesenchymal stromal cells (MSC-Exos) significantly mitigated colitis in various models of IBD. MSC-Exos treatment downregulated inflammatory responses, maintained intestinal barrier integrity and polarized M2b macrophages, but did not favor intestinal fibrosis. Mechanistically, infused MSC-Exos mainly acted on colonic macrophages and macrophages from colitic colons acquired obvious resistance to inflammatory re-stimulation when prepared from mice treated with MSC-Exos versus untreated mice. The beneficial effect of MSC-Exos was blocked by macrophage depletion. Besides, the induction of IL-10 production from macrophages was partially involved in the beneficial effect of MSC-Exos. MSC-Exos were enriched in proteins involved in regulating multiple biological processes associated with the anti-colitic benefit of MSC-Exos. Particularly, metallothionein-2 in MSC-Exos was required for the suppression of inflammatory responses. Taken together, MSC-Exos are critical regulators of inflammatory responses and may be promising candidates for IBD treatment.