间充质干细胞
免疫学
超氧化物歧化酶
医学
促炎细胞因子
炎症
贾纳斯激酶
特应性皮炎
干细胞
免疫系统
癌症研究
细胞因子
生物
病理
细胞生物学
内科学
氧化应激
作者
Shyam Kishor Sah,Gaurav Agrahari,Cattien V. Nguyen,Yeon‐Soo Kim,Kyung‐Sun Kang,Tae‐Yoon Kim
出处
期刊:Allergy
[Wiley]
日期:2018-08-24
卷期号:73 (12): 2364-2376
被引量:36
摘要
Abstract Background The use of mesenchymal stem cells ( MSC s) has been proposed to treat various autoimmune diseases. However, effective strategies for treating atopic dermatitis ( AD ) are still lacking, and the mechanisms underlying stem cell therapy remain largely unknown. In this study, we sought to explore potential clinical application of superoxide dismutase 3‐transduced MSC s ( SOD 3‐ MSC s) to experimental AD ‐like skin inflammation in in vitro and in vivo and its underlying anti‐inflammatory mechanisms. Methods SOD 3‐ MSC s were administered subcutaneously to mice with AD , and associated symptoms and biologic changes were evaluated. Human keratinocytes, mast cells, and murine T helper (Th) 2 cells were cocultured in vitro with SOD 3‐ MSC s to investigate potential therapeutic effects of SOD 3‐ MSC s. Results In mice with AD , SOD 3‐ MSC s ameliorated AD pathology and enhanced the efficacy of MSC therapy by controlling activated immune cells, by reducing expression levels of proinflammatory mediators in the skin, and by inhibiting the histamine H 4 receptor (H4R)‐mediated inflammatory cascade and activation of Janus kinase signal transducer and activator of transcription pathways. Similarly, coculture of SOD 3‐ MSC s with mast cells, keratinocytes, and Th2 cells effectively dampened H4R‐dependent persistent inflammatory responses by multiple mechanisms. Moreover, we also showed that SOD 3 interacts with H4R and IL ‐4 receptor α. The functional significance of this interaction could be a markedly reduced inflammatory response in keratinocytes and overall AD pathogenesis, representing a novel mechanism for SOD 3's anti‐inflammatory effects. Conclusion SOD 3‐ MSC s can be potentially used as an effective and clinically relevant therapy for AD and other autoimmune disorders.
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