title: miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis.
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.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Al-Mossawi
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ridley
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: T
authors.initials: T
authors.lastname: Sekine
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.|Department of Nephrology, Klinikum rechts der lsar, Technical University of Munich, Munich, Germany.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-2658-4764
authors.initials: A
authors.lastname: Hammitzsch
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: de Wit
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Simone
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: F
authors.initials: F
authors.lastname: Penkava
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kurowska-Stolarska
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Pulyakhina
authors.affiliation: Nuffield Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Knight
authors.affiliation: Department of Rheumatology, Medical School and Hospital, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: T J
authors.identifier: http://orcid.org/0000-0002-2871-1635
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.|National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bowness
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D013167:Spondylitis, Ankylosing; D058504:Th17 Cells / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D055815:Young Adult; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D020930:MAP Kinase Kinase Kinases; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C508717:IL17A protein, human; C547183:MIRN10 microRNA, human; C524942:MIRN155 microRNA, human; C543800:MIRN210 microRNA, human
keywords: Ankylosing Spondylitis; Cytokines; T Cells