Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.
Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.
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人脐带间充质干细胞通过将巨噬细胞极化为抗炎表型来缓解兔子持续的自身免疫性泪腺炎。
DOI：
10.1016/j.exer.2019.107905
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发表时间：
2020-03
影响因子：
3.4
通讯作者：
Wei R
中科院分区：
文献类型：
--
作者：
Lu X;Li N;Zhao L;Guo D;Yi H;Yang L;Liu X;Sun D;Nian H;Wei R
间充质干细胞(MSCs)对自身免疫性泪腺炎有良好的治疗效果。然而，其潜在的机制还没有完全被理解。本研究观察了人脐带间充质干细胞(Huc-MSCs)对干燥综合征(SS)干眼动物模型兔自身免疫性泪囊炎的治疗作用，并探讨其对巨噬细胞极化的调节作用。我们的研究表明，发病后全身输注Huc-MSCs可有效减轻病变LGs的慢性炎症反应，改善临床症状。进一步分析发现，Huc-MSC可显著抑制LGs中促炎性M_1巨噬细胞标志物iNOS、肿瘤坏死因子-α和IL-6的表达，促进抗炎性M_2巨噬细胞标志物Arg1、CD206、IL-10、IL-4和转化生长因子-β的表达。在机制上，Huc-MSCs激活巨噬细胞中的AKT通路，导致M2相关分子Arg1上调，该上调可被PI3K抑制剂LY294002部分阻断。综上所述，我们的数据表明Huc-MSCs可以通过影响AKT途径使巨噬细胞向M2表型倾斜。这些数据可能为研究Huc-MSCs治疗SS干眼的机制提供新的思路。
Mesenchymal stem cells (MSCs) exhibit beneficial effects on autoimmune dacryoadenitis. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on rabbit autoimmune dacryoadenitis, an animal model of Sjögren’s syndrome (SS) dry eye, and explored whether the effects of MSCs were related to their modulation on macrophage polarization. We have showed that systemic infusion of hUC-MSCs after disease onset efficiently diminished the chronic inflammation in diseased LGs and improved the clinical symptoms. Further analysis revealed that hUC-MSC treatment significantly inhibited the expression of pro-inflammatory M1 macrophage markers iNOS, TNF-α and IL-6, and promoted the expression of anti-inflammatory M2 macrophage markers Arg1, CD206, IL-10, IL-4 and TGF-β in LGs. Mechanistically, hUC-MSCs activated AKT pathway in macrophages, resulting in upregulation of M2-associated molecule Arg1, which was partly abolished by PI3K inhibitor, LY294002. Together, our data indicated that hUC-MSCs can skew macrophages into an M2 phenotype via affecting AKT pathway. These data may provide a new insight into the mechanisms of hUC-MSCs in the therapy of SS dry eye.
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DOI：
10.1073/pnas.1522905113
发表时间：
2016-01-05
影响因子：
11.1
作者：
Ko, Jung Hwa;Lee, Hyun Ju;Oh, Joo Youn
通讯作者：
Oh, Joo Youn
影响因子：
5.2
作者：
Chiossone, Laura;Conte, Romana;Bottino, Cristina
通讯作者：
Bottino, Cristina
影响因子：
10.8
作者：
Ma, Yonggang;Chiao, Ying Ann;Jin, Yu-Fang
通讯作者：
Jin, Yu-Fang
影响因子：
4.4
作者：
Li, Xiaodong;Wu, Kaijin;Hamm-Alvarez, Sarah F.
通讯作者：
Hamm-Alvarez, Sarah F.
间充质干细胞衍生的外泌体对实验性自身免疫性葡萄膜炎的影响
影响因子：
4.6
作者：
Bai L;Shao H;Wang H;Zhang Z;Su C;Dong L;Yu B;Chen X;Li X;Zhang X
通讯作者：
Zhang X