miR-10b-5p 是一种新型的 Th17 调节因子，存在于强直性脊柱炎患者的 Th17 细胞中。
miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis.
机构信息
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Department of Nephrology, Klinikum rechts der lsar, Technical University of Munich, Munich, Germany.
出版信息
Ann Rheum Dis. 2017 Mar;76(3):620-625. doi: 10.1136/annrheumdis-2016-210175. Epub 2016 Dec 30.
OBJECTIVE
To determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells.
METHODS
Interleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays.
RESULTS
AS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells.
CONCLUSIONS
AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS.
目的
确定强直性脊柱炎（AS）辅助性 T 细胞 17（Th17）细胞中的 microRNA（miR）特征。
方法
采用流式细胞分选技术从 AS 患者和健康对照者的白细胞介素（IL）-17A 产生 CD4+T 细胞中进行 miR 测序和 qPCR 验证。通过 miR 模拟物表达确定 miR-10b 的功能，然后进行细胞因子测量、转录组分析、qPCR 和荧光素酶测定。
结果
AS Th17 细胞表现出 miR 特征，特征为 miR-155-5p、miR-210-3p 和 miR-10b 的上调。miR-10b 以前未在 Th17 细胞中描述过，因此选择其进行进一步表征。miR-10b 在体外分化的 Th17 细胞中被短暂诱导。转录组、qPCR 和荧光素酶测定表明，MAP3K7 是 miR-10b 的靶标。miR-10b 过表达和 MAP3K7 沉默均抑制总 CD4 和分化的 Th17 细胞产生 IL-17A。
结论
AS Th17 细胞具有特定的 miR 特征，并在体外上调 miR-10b。我们的数据表明，miR-10b 被促炎细胞因子上调，并通过靶向 MAP3K7 可能作为抑制 IL-17A 的反馈回路。miR-10b 是一种有潜力的治疗候选物，可抑制 AS 患者致病性 Th17 细胞功能。
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