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

Chen, L. et al. (2017) miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis. Annals of the Rheumatic Diseases, 76(3), pp. 620-624. (doi:10.1136/annrheumdis-2016-210175) (PMID:28039186)

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Abstract

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.

Item Type:Articles
Additional Information:Funding: Wellcome Trust; Arthritis Research UK (grant nos. 20235, 20773); National Institute for Health Research (Oxford Biomedical Research Centre and Unit); Deutsche Forschungsgemeinschaft (grant no. HA-7021/1-1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurowska-Stolarska, Dr Mariola
Authors: Chen, L., Al-Mossawi, M.H., Ridley, A., Sekine, T., Hammitzsch, A., de Wit, J., Simone, D., Shi, H., Penkava, F., Kurowska-Stolarska, M., Pulyakhina, I., Knight, J.C., Kim, T.J., and Bowness, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
Publisher:BMJ Publishing Group
ISSN:0003-4967
ISSN (Online):1468-2060
Published Online:30 December 2016

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