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

Ilan Ben-Zvi, Cynthia Aranow, Meggan Mackay, Anfisa Stanevsky, Diane L. Kamen, L. Manuela Marinescu, Christopher E. Collins, Gary S. Gilkeson, Betty Diamond, John A. Hardin

Research output: Contribution to journalArticle

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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 IFNα 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 IFNα-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=-2.234, 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 IFNα-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 IFNα activity in vivo and, most importantly, improves clinical outcome.

Original languageEnglish (US)
Article numbere9193
JournalPLoS One
Volume5
Issue number2
DOIs
StatePublished - Feb 16 2010

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lupus erythematosus
dendritic cells
vitamin D
Vitamin D
Systemic Lupus Erythematosus
Dendritic Cells
vitamin D deficiency
Vitamin D Deficiency
Chemical activation
monocytes
Monocytes
Genes
Tissue Donors
African Americans
Hispanic Americans
Amplification
clinical trials
homeostasis
Homeostasis
genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ben-Zvi, I., Aranow, C., Mackay, M., Stanevsky, A., Kamen, D. L., Marinescu, L. M., ... Hardin, J. A. (2010). The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. PLoS One, 5(2), [e9193]. https://doi.org/10.1371/journal.pone.0009193

The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. / Ben-Zvi, Ilan; Aranow, Cynthia; Mackay, Meggan; Stanevsky, Anfisa; Kamen, Diane L.; Marinescu, L. Manuela; Collins, Christopher E.; Gilkeson, Gary S.; Diamond, Betty; Hardin, John A.

In: PLoS One, Vol. 5, No. 2, e9193, 16.02.2010.

Research output: Contribution to journalArticle

Ben-Zvi, I, Aranow, C, Mackay, M, Stanevsky, A, Kamen, DL, Marinescu, LM, Collins, CE, Gilkeson, GS, Diamond, B & Hardin, JA 2010, 'The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus', PLoS One, vol. 5, no. 2, e9193. https://doi.org/10.1371/journal.pone.0009193
Ben-Zvi I, Aranow C, Mackay M, Stanevsky A, Kamen DL, Marinescu LM et al. The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. PLoS One. 2010 Feb 16;5(2). e9193. https://doi.org/10.1371/journal.pone.0009193
Ben-Zvi, Ilan ; Aranow, Cynthia ; Mackay, Meggan ; Stanevsky, Anfisa ; Kamen, Diane L. ; Marinescu, L. Manuela ; Collins, Christopher E. ; Gilkeson, Gary S. ; Diamond, Betty ; Hardin, John A. / The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. In: PLoS One. 2010 ; Vol. 5, No. 2.
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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 IFNα 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 IFNα-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=-2.234, 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 IFNα-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 IFNα activity in vivo and, most importantly, improves clinical outcome.",
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