title: Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity.
  
  
  METHODS
  Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays.
  
  
  RESULTS
  Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a.
  
  
  CONCLUSIONS
  Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Haupt
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Kreuzer
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Hammitzsch
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Proft
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Carla
authors.initials: C
authors.lastname: Neumann
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Leipe
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Witt
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: Alla
authors.initials: A
authors.lastname: Skapenko
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
keywords: Autoimmune Diseases; Rheumatoid Arthritis; T Cells