title: The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients.
abstract: BACKGROUND
  Vitamin D has regulatory effects on innate and adaptive immunity. Curiously, hereditary vitamin D-resistant rickets (HVDRR) patients show no increased incidence of infectious or autoimmune diseases.
  
  
  OBJECTIVE
  The aim of the study was to investigate the role of vitamin D and the vitamin D receptor (VDR) in innate and adaptive immune responses in monocytes and lymphocytes from HVDRR patients.
  
  
  METHODS
  Fifteen HVDRR patients and 17 controls participated in the investigation. Activated monocytes (lipopolysaccharides) and lymphocytes (anti-CD3, CD28, and α-GalCer) were incubated with and without 25(OH)D3 (100 nM). The mRNA expressions of CYP27B1 and VDR; vitamin D response (TLR2); vitamin D response elements binding protein (hnRNP); antimicrobial peptides cathelicidin and β-defensin; the transcription factor enhancer binding proteins C/EBPα, C/EBPβ, and C/EBPε and enzymes involved in NO generation, Nos2, and Arginase1 were analyzed by RT-PCR. TNF-α, interferon-γ, IL-4, IL-10, and IL-17 concentrations in lymphocyte cultures media were measured by ELISA.
  
  
  RESULTS
  Cathelicidin expression was lower in HVDRR monocytes than in control monocytes. 25(OH)D3 increased significantly the expression of cathelicidin in control monocytes (2.3-fold) but only slightly in HVDRR monocytes. 25(OH)D3 increased the expression of VDR (2-fold), C/EBPε (2-fold), C/EBPβ (1.7-fold), and hnRNP and suppressed TLR2 only in control monocytes. Unexpectedly, 25(OH)D3 increased the expression of CYP27b1, C/EBPα, Nos2, and Arginase1 in HVDRR monocytes. TNFα and IL-17 concentrations were significantly higher in HVDRR lymphocyte cultures than in controls. 25(OH)D3 suppressed IL-17 only in control lymphocyte. 25(OH)D3 increased IL-4, IL-10, and interferon-γ concentrations in control lymphocyte media but not in HVDRR.
  
  
  CONCLUSIONS
  Our results demonstrate impairments in various components of innate immunity in HVDTRR patients' monocytes and a proinflammatory cytokine profile in their lymphocytes. The underlying VDR-independent compensatory mechanisms that protect HVDRR patients from infections and autoimmune diseases remain undetermined.
authors.affiliation: Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. d_tiosano@rambam.health.gov.il
authors.forename: Dov
authors.initials: D
authors.lastname: Tiosano
authors.forename: Gizi
authors.initials: G
authors.lastname: Wildbaum
authors.forename: Vardit
authors.initials: V
authors.lastname: Gepstein
authors.forename: Oleg
authors.initials: O
authors.lastname: Verbitsky
authors.forename: Yosef
authors.initials: Y
authors.lastname: Weisman
authors.forename: Nathan
authors.initials: N
authors.lastname: Karin
authors.forename: Amos
authors.initials: A
authors.lastname: Eztioni
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol