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.

中文翻译：

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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正在进行的自身免疫性泪腺炎。

间充质干细胞 (MSC) 对自身免疫性泪腺炎表现出有益作用。然而，潜在的机制尚未完全了解。在本研究中，我们研究了人脐带间充质干细胞 (hUC-MSCs) 对兔自身免疫性泪腺炎（一种干燥综合征（SS）干眼症的动物模型）的治疗作用，并探讨了 MSCs 的作用是否与其调节有关关于巨噬细胞极化。我们已经表明，在疾病发作后全身输注 hUC-MSC 可有效减少患病 LG 的慢性炎症并改善临床症状。进一步分析显示，hUC-MSC处理显着抑制促炎M1巨噬细胞标志物iNOS、TNF-α和IL-6的表达，促进抗炎M2巨噬细胞标志物Arg1、CD206、LGs 中的 IL-10、IL-4 和 TGF-β。从机制上讲，hUC-MSCs 激活巨噬细胞中的 AKT 通路，导致 M2 相关分子 Arg1 的上调，这被 PI3K 抑制剂 LY294002 部分消除。总之，我们的数据表明 hUC-MSCs 可以通过影响 AKT 途径将巨噬细胞扭曲成 M2 表型。这些数据可能为 hUC-MSCs 在 SS 干眼治疗中的机制提供新的见解。