The Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, Jiangdongbei Road 88, Nanjing, 210036 Jiangsu Province, China.
School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013 Jiangsu Province, China.
J Immunol Res. 2020 Mar 20;2020:4184380. doi: 10.1155/2020/4184380. eCollection 2020.
T helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an important regulator in the type 2 cytokine (IL-4, IL-5, and IL-13) immune response. However, it is unknown whether 7P regulates Th9 cell differentiation during ovalbumin- (OVA-) induced allergic lung inflammation. To address this, we studied wild-type mice treated with 7P and a control peptide in an mouse model of OVA-induced allergic inflammation and an cell model of Th9 differentiation, using flow cytometry, cytokine assays, and quantitative PCR. The binding of 7P to CD81 on naïve CD4 T cells during lung Th9 differentiation was determined using CD81 overexpression and siRNA knockdown analyses. Administration of 7P significantly reduced Th9 cell differentiation after OVA sensitization and exposure. 7P also inhibited Th9 cell differentiation from naïve and memory CD4 T cells . Furthermore, 7P inhibited the differentiation of human Th9 cells with high CD81 expression from naïve CD4 T cells by blocking CD81 signaling. CD81 siRNA significantly reduced Th9 cell differentiation from naïve CD4 T cells . Interestingly, CD81 overexpression in human naïve CD4 T cells also enhanced Th9 development . These data indicate that 7P may be a good candidate for reducing IL-9 production in asthma.
辅助性 T 细胞（Th）在哮喘发病机制中协调过敏性肺炎症。Th9 是一种新型的 Th 细胞亚群，主要产生白细胞介素-9（IL-9），这是哮喘中的一种强有力的促炎细胞因子。丙型肝炎病毒高变区 1（HVR1）的 7 个氨基酸肽（7P）已被确定为 2 型细胞因子（IL-4、IL-5 和 IL-13）免疫反应的重要调节剂。然而，尚不清楚 7P 是否调节卵清蛋白（OVA）诱导的过敏性肺炎症期间 Th9 细胞分化。为了解决这个问题，我们使用流式细胞术、细胞因子测定和定量 PCR，在 OVA 诱导的过敏炎症小鼠模型和 Th9 分化的 细胞模型中研究了用 7P 和对照肽处理的野生型小鼠。使用 CD81 过表达和 siRNA 敲低分析确定了 7P 在肺 Th9 分化过程中与 naïve CD4 T 细胞上的 CD81 结合。7P 给药可显著减少 OVA 致敏和暴露后 Th9 细胞的分化。7P 还抑制了从幼稚和记忆 CD4 T 细胞分化而来的 Th9 细胞分化。此外，7P 通过阻断 CD81 信号抑制了高 CD81 表达的人 Th9 细胞从幼稚 CD4 T 细胞的分化。CD81 siRNA 显著减少了幼稚 CD4 T 细胞中的 Th9 细胞分化。有趣的是，人幼稚 CD4 T 细胞中的 CD81 过表达也增强了 Th9 细胞的发育。这些数据表明，7P 可能是减少哮喘中 IL-9 产生的一个很好的候选物。
