Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan.
School of Medicine, Tzu Chi University, Hualien City, Taiwan.
Arthritis Res Ther. 2018 Nov 21;20(1):259. doi: 10.1186/s13075-018-1754-1.
Interleukin (IL)-23 can facilitate the differentiation of IL-17-producing helper T cells (Th17). The IL-23/IL-17 axis is known to play a key role in the immunopathogenesis of ankylosing spondylitis (AS). We hypothesized that the expression of microRNAs (miRNAs, miRs) would be regulated by IL-23 and that these miRNAs could participate in the immunopathogenesis of AS.
Expression profiles of human miRNAs in K562 cells, cultured in the presence or absence of IL-23 for 3 days, were analyzed by microarray. Potentially aberrantly expressed miRNAs were validated using T-cell samples from 24 patients with AS and 16 control subjects. Next-generation sequencing (NGS) was conducted to search for gene expression and biological functions regulated by specific miRNAs in the IL-23-mediated signaling pathway.
Initial analysis revealed that the expression levels of 12 miRNAs were significantly higher, whereas those of 4 miRNAs were significantly lower, in K562 cells after coculture with IL-23 for 3 days. Among these IL-23-regulated miRNAs, the expression levels of miR-29b-1-5p, miR-4449, miR-211-3p, miR-1914-3p, and miR-7114-5p were found to be higher in AS T cells. The transfection of miR-29b-1-5p mimic suppressed IL-23-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation in K562 cells. After NGS analysis and validation, we found that miR-29b-1-5p upregulated the expression of angiogenin, which was also upregulated in K562 cells after coculture with IL-23. Increased expression of miR-29b-1-5p or miR-211-3p could enhance interferon-γ expression.
Among the miRNAs regulated by IL-23, expression levels of five miRNAs were increased in T cells from patients with AS. The transfection of miR-29b-1-5p mimic could inhibit the IL-23-mediated STAT3 phosphorylation and might play a role in negative feedback control in the immunopathogenesis of AS.
白细胞介素 (IL)-23 可促进 IL-17 产生辅助性 T 细胞 (Th17) 的分化。IL-23/IL-17 轴在强直性脊柱炎 (AS) 的免疫发病机制中起着关键作用。我们假设微 RNA（miRNAs，miRs）的表达受 IL-23 调控，这些 miRNAs 可能参与 AS 的免疫发病机制。
通过微阵列分析了在存在或不存在 IL-23 的情况下培养 3 天的 K562 细胞中人类 miRNAs 的表达谱。使用来自 24 例 AS 患者和 16 例对照的 T 细胞样本验证潜在异常表达的 miRNAs。进行下一代测序 (NGS) 以搜索特定 miRNAs 在 IL-23 介导的信号通路中调控的基因表达和生物学功能。
初步分析显示，与未用 IL-23 共培养的 K562 细胞相比，与 IL-23 共培养 3 天后，12 种 miRNAs 的表达水平显著升高，而 4 种 miRNAs 的表达水平显著降低。在这些受 IL-23 调控的 miRNAs 中，miR-29b-1-5p、miR-4449、miR-211-3p、miR-1914-3p 和 miR-7114-5p 在 AS T 细胞中的表达水平升高。miR-29b-1-5p 模拟物的转染抑制了 K562 细胞中 IL-23 介导的信号转导和转录激活因子 3（STAT3）磷酸化。经过 NGS 分析和验证，我们发现 miR-29b-1-5p 上调了血管生成素的表达，而血管生成素在与 IL-23 共培养的 K562 细胞中也上调。miR-29b-1-5p 或 miR-211-3p 的表达增加可增强干扰素-γ的表达。
在受 IL-23 调控的 miRNAs 中，AS 患者 T 细胞中五种 miRNAs 的表达水平升高。miR-29b-1-5p 模拟物的转染可抑制 IL-23 介导的 STAT3 磷酸化，可能在 AS 的免疫发病机制中发挥负反馈控制作用。
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