title: Influence of 1 Alpha, 25-Dihydroxyvitamin D3 on T Helper 17 Cells and Related Cytokines in Systemic Lupus Erythematosus.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor.
  
  
  OBJECTIVE
  To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients.
  
  
  METHODS
  Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF-β genes were assessed by real-time PCR.
  
  
  RESULTS
  The percentage of Th17 cells (CD3+CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%)( p=0.003). The expression of TGF-β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment.
  
  
  CONCLUSIONS
  This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity.
authors.affiliation: Immunology Research Center, BuAli Research Institute, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, e-mail: RDRC@mums.ac.ir.
authors.forename: Hadi
authors.initials: H
authors.lastname: Reihani
authors.forename: Maryam
authors.initials: M
authors.lastname: Rastin
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ghoryani
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Abdollahi
authors.forename: Nafiseh Sadat
authors.initials: NS
authors.lastname: Tabasi
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Zamani Taghizadeh Rabe
authors.forename: Maryam
authors.initials: M
authors.lastname: Sahebari
mesh_terms: D000328:Adult; D020126:Brefeldin A / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C508717:IL17A protein, human; C508840:IL23A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D020126:Brefeldin A; D015759:Ionomycin; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate