The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus

PLoS One. 2010 Feb 16;5(2):e9193. doi: 10.1371/journal.pone.0009193.

Abstract

Background: Excessive activity of dendritic cells (DCs) is postulated as a central disease mechanism in Systemic Lupus Erythematosus (SLE). Vitamin D is known to reduce responsiveness of healthy donor DCs to the stimulatory effects of Type I IFN. As vitamin D deficiency is reportedly common in SLE, we hypothesized that vitamin D might play a regulatory role in the IFNalpha amplification loop in SLE. Our goals were to investigate the relationship between vitamin D levels and disease activity in SLE patients and to investigate the effects of vitamin D on DC activation and expression of IFNalpha-regulated genes in vitro.

Methodology/principal findings: In this study, 25-OH vitamin D (25-D) levels were measured in 198 consecutively recruited SLE patients. Respectively, 29.3% and 11.8% of African American and Hispanic SLE patient had 25-D levels <10 ng/ml. The degree of vitamin D deficiency correlated inversely with disease activity; R = -.234, p = .002. In 19 SLE patients stratified by 25-D levels, there were no differences between circulating DC number and phenotype. Monocyte-derived DCs (MDDCs) of SLE patients were normally responsive to the regulatory effects of vitamin D in vitro as evidenced by decreased activation in response to LPS stimulation in the presence of 1,25-D. Additionally, vitamin D conditioning reduced expression of IFNalpha-regulated genes by healthy donor and SLE MDDCs in response to factors in activating SLE plasma.

Conclusions/significance: We report on severe 25-D deficiency in a substantial percentage of SLE patients tested and demonstrate an inverse correlation with disease activity. Our results suggest that vitamin D supplementation will contribute to restoring immune homeostasis in SLE patients through its inhibitory effects on DC maturation and activation. We are encouraged to support the importance of adequate vitamin D supplementation and the need for a clinical trial to assess whether vitamin D supplementation affects IFNalpha activity in vivo and, most importantly, improves clinical outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • African Americans / statistics & numerical data
  • Aged
  • Antigens / genetics
  • Asians / statistics & numerical data
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Child
  • Cytoskeletal Proteins / genetics
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Female
  • Flow Cytometry
  • GTP-Binding Proteins / genetics
  • Gene Expression / drug effects
  • Hispanic or Latino / statistics & numerical data
  • Humans
  • Immunophenotyping
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / ethnology
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Middle Aged
  • Myxovirus Resistance Proteins
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitamin D / blood*
  • Vitamin D / pharmacology
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / ethnology
  • Whites / statistics & numerical data
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens
  • Carrier Proteins
  • Cytoskeletal Proteins
  • IFI44 protein, human
  • IFIT1 protein, human
  • Myxovirus Resistance Proteins
  • RNA-Binding Proteins
  • Vitamin D
  • GTP-Binding Proteins