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J Clin Endocrinol Metab. 2013 Apr;98(4):1685-93. doi: 10.1210/jc.2012-3858. Epub 2013 Mar 12.

The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients.

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  • 1Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. d_tiosano@rambam.health.gov.il

Abstract

CONTEXT:

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.

OBJECTIVES:

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.

DESIGN AND 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.

PMID:
23482605
[PubMed - indexed for MEDLINE]
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