Department of Oral Medicine, School of Stomatology, Capital Medical University, Beijing, China.
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.
J Oral Pathol Med. 2018 Apr;47(4):425-433. doi: 10.1111/jop.12690. Epub 2018 Mar 6.
This study was to investigate association and potentially destructive role of Th9/IL-9 and their synergistic interaction with Th17 cells in elevating MMP9 production in local lesions of oral lichen planus (OLP) patients.
Oral mucosal tissues were obtained from OLP patients and healthy controls (HC) and then divided into an epithelial part (EP) or a lamina propria part (LP). Both EP and LP subsets were assessed for IL-9 and MMP9 mRNA levels by real-time quantitative PCR (qPCR). Flow cytometry was used to detect the CD4+ T helper subset Th9 (IL-9 IL-17 CD4 ) and Th17 (IL-9 IL-17 CD4 ) in co-cultured CD4+ Th cells and oral keratinocytes of OLP. IL-9, IL-17, and MMP9 in co-culture supernatant were detected by ELISA.
The qPCR results demonstrated that IL-9 and MMP9 mRNA levels were positively correlated in OLP lesions, and both significantly elevated in EP and LP lesions of erosive type OLP. Th9 and Th17 cells were significantly elevated in co-cultures of CD4+ Th cells and keratinocytes, and MMP9, IL-9, and IL-17 levels were simultaneously increased. In vitro, recombinant human IL-17 treatment significantly enhanced MMP9 protein and mRNA levels, while a synergistic effect of IL-9 and IL-17 was not observed. However, further results showed Th17 cells, IL-17, and MMP9 were increased significantly when recombinant IL-9 was added to the cultured CD4+ T cells.
This study demonstrated that Th9/IL-9 can induce elevated levels of MMP9 to aggravate OLP disease severity, which may occur directly through increasing Th17 levels or indirectly through a synergistic role with Th17.
本研究旨在探讨 Th9/IL-9 的关联及其对 MMP9 产生的潜在破坏性作用，以及其与 Th17 细胞的协同作用在提升口腔扁平苔藓（OLP）患者局部病变中 MMP9 产生的作用。
从 OLP 患者和健康对照者（HC）的口腔黏膜组织中获取组织，然后将其分为上皮部分（EP）或固有层部分（LP）。通过实时定量 PCR（qPCR）评估 EP 和 LP 亚群中的 IL-9 和 MMP9 mRNA 水平。流式细胞术用于检测共培养的 CD4+T 辅助细胞 Th9（IL-9+IL-17+CD4+）和 OLP 口腔角质形成细胞中的 Th17（IL-9+IL-17+CD4+）。通过 ELISA 检测共培养上清液中的 IL-9、IL-17 和 MMP9。
qPCR 结果表明，在 OLP 病变中，IL-9 和 MMP9 mRNA 水平呈正相关，且在糜烂型 OLP 的 EP 和 LP 病变中均显著升高。在 CD4+Th 细胞和角质形成细胞的共培养中，Th9 和 Th17 细胞显著升高，同时 MMP9、IL-9 和 IL-17 水平也同时升高。在体外，重组人 IL-17 治疗显著增强了 MMP9 蛋白和 mRNA 水平，而未观察到 IL-9 和 IL-17 的协同作用。然而，进一步的结果表明，当向培养的 CD4+T 细胞中添加重组 IL-9 时，Th17 细胞、IL-17 和 MMP9 水平显著升高。
本研究表明，Th9/IL-9 可诱导 MMP9 水平升高，从而加重 OLP 疾病严重程度，其可能通过增加 Th17 水平或通过与 Th17 的协同作用而直接发生。
