IL-17A预处理促进间充质干细胞来源的外泌体携带lncRNA NEAT1及缓解缺血再灌注肾损伤的机制研究

缺血再灌注肾损伤（IRI-AKI）是急性肾损伤的常见病因，炎症反应是其重要机制。我们前期证实白介素-17A（IL-17A）可促进间充质干细胞（MSCs）诱导调节性T细胞（Treg）分化、提高MSCs治疗IRI-AKI疗效。但直接应用活细胞仍面临诸多限制。我们通过预实验发现IL-17A同样能促进MSCs来源的外泌体（MSC-Exo）诱导Treg分化、提高其治疗IRI-AKI的疗效，且lncRNA NEAT1在此过程中有重要作用。生信分析示IL-17A下游NF-κB可转录调控NEAT1，Treg分化中的重要分子miR-27是NEAT1的靶分子。据此推测：IL-17A或通过NF-κB促进MSC-Exo携带NEAT1，进而调控miR-27、促进Treg分化、抑制炎症反应，缓解IRI-AKI。本课题将为阐明MSC-Exo治疗IRI-AKI机制、寻找IRI-AKI防治新策略提供理论依据。

Ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI). Inflammation plays an important role on the occurrence and prognosis of IRI-AKI. Previously, we found out that IL-17A-pretreatment could improve the regulatory T cell (Treg) induction and immunosuppression efficacy of mesenchymal stem cells (MSC), and the efficacy of MSCs on IRI-AKI. However, the direct use of IL-17A-MSCs in vivo had the same limitations of the use of living cells. Furthermore, we found out that IL-17A pretreatment could improve the efficacy of MSC-derived exosome (MSC-Exo) on Treg induction and IRI-AKI mice treatment as well. Additionally, we found out that lncRNA NEAT1 had a important role on the efficacy improvement of IL-17A-MSC-Exo. Previous studies had proved that NF-κB was one of the important transcription factors of IL-17A. The bioinformatics analysis demonstrated that NF-κB could bind the promoter region of lncRNA NEAT1. Moreover, miR-27 was proved to have a critical role on Treg differentiation. And, we furtherly found out that miR-27 was one of the potential target moleculars of lncRNA NEAT1. Therefore, we proposed that IL-17A pretreatment could increase the expression of lncRNA NEAT1 of the MSC-Exo and the IL-17A-MSC-Exo could induce the Treg differentiation, suppress the inflammatory response, and improve the IRI-AKI by targeting miR-27. Our present study will clarify the mechanism of IL-17A-MSC-Exo on IRI-AKI. Most likely, the conclusions of our present study would provide important evidence and theory for the development of new treatment for IRI-AKI.