miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis.

Chen L., Al-Mossawi MH., Ridley A., Sekine T., Hammitzsch A., de Wit J., Simone D., Shi H., Penkava F., Kurowska-Stolarska M., Pulyakhina I., Knight JC., Kim TJ., Bowness P.

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.

DOI

10.1136/annrheumdis-2016-210175

Type

Journal article

Journal

Ann rheum dis

Publication Date

03/2017

Volume

76

Pages

620 - 625

Keywords

Ankylosing Spondylitis, Cytokines, T Cells, Adult, Aged, CD4-Positive T-Lymphocytes, Case-Control Studies, Cells, Cultured, Female, Gene Silencing, Humans, Interleukin-17, Interleukin-6, MAP Kinase Kinase Kinases, Male, MicroRNAs, Middle Aged, Spondylitis, Ankylosing, Th17 Cells, Transcriptome, Tumor Necrosis Factor-alpha, Up-Regulation, Young Adult

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