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.
- Ankylosing Spondylitis
- T Cells
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Handling editor Tore K Kvien
TJK and PB contributed equally.
Correction notice This article has been corrected since it published Online First. The 10th author's name has been corrected.
Contributors PB, LC, TJK, JCK and MKS designed the study. LC, TJK, MHA, AR, TS, AH, DS, HS, FP and IP carried out the experimental work. LC, TJK and PB wrote the manuscript.
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).
Competing interests PB has received research funding from Merck Laboratories and Celgene.
Patient consent Obtained.
Ethics approval Oxford Rec REC06/Q1606/139.
Provenance and peer review Not commissioned; externally peer reviewed.
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