人骨髓间充质干细胞来源的外泌体通过调控 miR-146a-5p/SERPINB2 通路抑制 Th2 细胞分化。

HMSC-Derived Exosome Inhibited Th2 Cell Differentiation via Regulating miR-146a-5p/SERPINB2 Pathway.

机构信息

Department of Otorhinolaryngology, Head & Neck Surgery, Dahua Hospital, Shanghai 200237, China.

Department of PharmaceuticsSchool of Pharmacy, Fudan University, Shanghai 201203, China.

出版信息

J Immunol Res. 2021 May 14;2021:6696525. doi: 10.1155/2021/6696525. eCollection 2021.

BACKGROUND

Allergic rhinitis (AR) is a global disease without specific treatment. Human mesenchymal stem cell- (HMSC-) derived exosomes (HMSC-exos) have been implicated for the amelioration of allergic inflammation by delivering miR-146a-5p in a mouse asthma model. However, the antiallergic activity and the underlying mechanism of HMSC-exos in AR remain unclear. The present study aimed to investigate the role of HMSC-exos in the pathogenesis of AR.

MATERIALS AND METHODS

Blood specimens were collected from AR patients and healthy donators for investigation. HMSC and CD4 T cells were used in the present study. Flow cytometry was used to characterize the population of Type 1 helper T (Th1) and Th2 cells. Specific siRNA and overexpressed plasmids were designed to silence or overexpress the expressions of miR-146a-5p and SERPINB2. Luciferase reporter assay was adopted to explore the binding site of miR-146a-5p and SERPINB2. Quantitative real-time PCR and immunoblots were performed to estimate the expression of target genes.

RESULTS

The population of Th2 cells was significantly elevated in AR patients as compared with that in healthy donators. HMSC-exos could decrease the expression of SERPINB2 and the differentiation of Th2 cells. miR-146a-5p in HMSC-exos exhibited consistent effects and lowered the expression of SERPINB2 by binding on its 3'UTR region. Moreover, the differentiation of Th2 cells was promoted by SERPINB2 that could be reversed by HMSC-exos. Additionally, the miR-146a-5p expression was negatively associated with the SERPINB2 expression in the serum of AR patients.

CONCLUSION

HMSC-exos could inhibit the differentiation of Th2 cells via the regulation of the miR-146a-5p/SERPINB2 pathway. miR-146a-5p and SERPINB2 could be applied as potential targets for AR treatment.

背景

过敏性鼻炎（AR）是一种全球性疾病，尚无特效疗法。在小鼠哮喘模型中，人骨髓间充质干细胞（HMSC）衍生的外泌体（HMSC-exos）通过递呈 miR-146a-5p 被认为可改善过敏性炎症。然而，HMSC-exos 在 AR 中的抗过敏活性及其潜在机制尚不清楚。本研究旨在探讨 HMSC-exos 在 AR 发病机制中的作用。

材料和方法

采集 AR 患者和健康供者的血液标本进行研究。本研究使用了 HMSC 和 CD4 T 细胞。流式细胞术用于鉴定 1 型辅助 T（Th1）和 Th2 细胞群。设计了特异性 siRNA 和过表达质粒以沉默或过表达 miR-146a-5p 和 SERPINB2 的表达。采用荧光素酶报告基因检测法探索 miR-146a-5p 和 SERPINB2 的结合位点。采用定量实时 PCR 和免疫印迹法评估靶基因的表达。

结果

与健康供者相比，AR 患者 Th2 细胞群显著升高。HMSC-exos 可降低 SERPINB2 表达和 Th2 细胞分化。HMSC-exos 中的 miR-146a-5p 表现出一致的作用，通过结合其 3'UTR 区域降低 SERPINB2 的表达。此外，SERPINB2 促进 Th2 细胞分化，而 HMSC-exos 可逆转这一作用。此外，AR 患者血清中 miR-146a-5p 的表达与 SERPINB2 的表达呈负相关。