miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis
miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis
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DOI：
10.1136/annrheumdis-2016-210175
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发表时间：
2017-03-01
影响因子：
27.4
通讯作者：
Bowness, P.
中科院分区：
文献类型：
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作者：
Chen, L.;Al-Mossawi, M. H.;Bowness, P.
目的检测强直性脊柱炎（AS）患者外周血T辅助细胞（Th）17细胞中的微小RNA（microRNA，miR）。结果AS Th17细胞中miR-155 - 5p、miR-210 - 3p和miR-10b表达上调，miR-210 - 3p和miR-210 - 3p表达上调。miR-10b先前在Th17细胞中未被描述，并被选择用于进一步表征。miR-10b在体外分化的Th17细胞中瞬时诱导。转录组、qPCR和荧光素酶测定表明，MAP3K7被miR-10b靶向。miR-10b过表达和MAP3K7沉默均抑制总CD4细胞和分化中的Th17细胞IL-17A的产生。我们的数据表明，miR-10 b是上调的促炎细胞因子，并可能作为一个反馈回路，通过靶向MAP3K7抑制IL-17 A。miR-10 b是一种潜在的治疗候选物，可抑制AS患者中致病性Th17细胞的功能。
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.