Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
Int J Mol Med. 2020 Aug;46(2):859-868. doi: 10.3892/ijmm.2020.4618. Epub 2020 May 27.
Long non‑coding RNA (lncRNAs) have been identified to play important roles in multiple human diseases via the regulation of cell proliferation, cell invasion, or cell death. However, little is known about the role of lncRNAs in the process of shifts in the Th17/Treg ratio during the progression of juvenile idiopathic arthritis (JIA). The aim of the present study was to determine the role of lncRNA RP11‑340F14.6 in the shifting of the Th17/Treg ratio in JIA. The distribution of the T cell subgroup was detected by flow cytometry in peripheral blood mononuclear cells from patients with JIA and healthy controls. It was found that the expression of lncRNA RP11‑340F14.6 was upregulated, and to positively correlate with that of retinoic acid‑related orphan receptor gamma t (RORγt), and to negatively correlate with Foxp3 expression in patients with JIA. RP11‑340F14.6 induced the expression of its neighbor, P2X7R. Through a P2X7R‑independent approach, this lncRNA was also found to play a pivotal role in stimulating Th17 differentiation and simultaneously suppressing Treg distribution. Taken together, the findings of the present study demonstrate that RP11‑340F14.6 specifically binds to P2X7R, which results in the continuous activation of P2X7R. Thus, RP11‑340F14.6 may serve as a promising therapeutic target for the treatment of JIA.
长链非编码 RNA（lncRNAs）已被鉴定通过调节细胞增殖、细胞侵袭或细胞死亡在多种人类疾病中发挥重要作用。然而，lncRNAs 在幼年特发性关节炎（JIA）进展过程中 Th17/Treg 比值变化过程中的作用知之甚少。本研究旨在确定 lncRNA RP11-340F14.6 在 JIA 中 Th17/Treg 比值变化中的作用。通过流式细胞术检测 JIA 患者和健康对照者外周血单个核细胞中 T 细胞亚群的分布。结果发现，lncRNA RP11-340F14.6 的表达上调，并与 JIA 患者中 retinoic acid-related orphan receptor gamma t（RORγt）的表达呈正相关，与 Foxp3 的表达呈负相关。RP11-340F14.6 诱导其相邻基因 P2X7R 的表达。通过一种 P2X7R 非依赖性方法，还发现这种 lncRNA 在刺激 Th17 分化和同时抑制 Treg 分布方面发挥着关键作用。综上所述，本研究结果表明，RP11-340F14.6 特异性结合 P2X7R，导致 P2X7R 的持续激活。因此，RP11-340F14.6 可能成为治疗 JIA 的有前途的治疗靶点。
