title: Effect of all-transretinoic acid on Th17 and T regulatory cell subsets in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  We compared Th17 and T regulatory cells in patients with ankylosing spondylitis (AS) and in healthy controls. The effect of all-transretinoic acid (ATRA) was studied on cultured CD4+ T cells of patients with AS compared to controls.
  
  
  METHODS
  Eighteen patients with AS and 18 age- and sex-matched healthy controls were included. CD4+ T cells were separated and cultured in conditions of anti-CD3 and anti-CD28 stimulation with and without ATRA. Intracellular and secreted cytokines, transcription factors, and gene expression were evaluated after 72 h.
  
  
  RESULTS
  The frequency of CD4+IL-17+ T cells was significantly higher in patients with AS compared to controls, and ATRA could significantly decrease it. The frequency of forkhead box protein 3 (FOXP3)+ retinoic acid-related orphan receptor γt (RORγt) negative T-bet negative CD4+ cells was significantly lower in cases compared to controls. Intracellular and secreted interferon-γ (IFN-γ) was not significantly different between cases and controls. ATRA significantly increased intracellular IFN-γ in cases but not in controls. Tumor necrosis factor-α (TNF-α) secretion was significantly higher and interleukin 10 secretion was significantly lower in culture supernatant of cases compared to controls. ATRA could significantly decrease TNF-α secretion in cases.
  
  
  CONCLUSIONS
  Our findings favor a pathogenic role for Th17 cells in AS. Th1 cells did not seem to contribute in the pathogenesis of this disease. The effect of ATRA as an immunomodulator on deviated immune cells was associated with decreased inflammatory markers. This association could be a reason for a clinical trial of ATRA in patients with AS.
authors: Immunology, Asthma and Allergy Research Institute, Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. kbidad@razi.tums.ac.ir
authors: Katayoon
authors: K
authors: Bidad
authors: Eisa
authors: E
authors: Salehi
authors: Ahmadreza
authors: A
authors: Jamshidi
authors: Ali Akbar
authors: AA
authors: Saboor-Yaraghi
authors: Mona
authors: M
authors: Oraei
authors: Alipasha
authors: A
authors: Meysamie
authors: Mahdi
authors: M
authors: Mahmoudi
authors: Mohammad Hossein
authors: MH
authors: Nicknam
mesh_terms: D000328:Adult; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014212:Tretinoin