miR-10b-5p is a novel Th17 regulator present in Th17 cells from Ankylosing Spondylitis

Journal article

Objective: to determine the microRNA (miR) signature in ankylosing spondylitis (AS) Th17 cells.

Methods: IL-17A-producing CD4+ T cells from AS patients and healthy controls were FACS-sorted for miR RNA 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 characterized 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 characterization. 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 over-expression 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 pro-inflammatory 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 AS patients.

Authors: Chen, L; Al-Mossawi, M; Ridley, A; Sekine, T; Hammitzsch, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Annals of the Rheumatic Diseases
• Volume: 76
• Issue: 3
• Pages: 620-625
• Publication date: 2017-02-17
• Acceptance date: 2016-12-03
• DOI: 10.1136/annrheumdis-2016-210175
• EISSN: 1468-2060
• ISSN: 0003-4967
• Keywords: cytokines; ankylosing spondylitis; T cells