Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

E. Zold, P. Szodoray, J. Kappelmayer, J. Gaal, L. Csathy, S. Barath, E. Gyimesi, A. Hajas, M. Zeher, G. Szegedi, E. Bodolay

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective: The aim of this study was to perform a quantitative and functional analysis of natural CD4+CD25highFoxp3+ regulatory T cells (nTregs) and CD4+IL-17+ T cells, and to assess the serum levels of proinflammatory cytokines in patients with undifferentiated connective tissue disease (UCTD) before and after 5 weeks of 0.5 μg/day alfacalcidol supplementation. Methods: Twenty-five patients with UCTD were enrolled in an open-label trial of alfacalcidol. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed by a high-performance liquid chromatography (HPLC) method. Flow cytometry was used for the quantification of nTregs and the IL-17 expression of T-helper (Th)17 cells. The serum concentrations of cytokines interleukin (IL)-12, interferon (IFN)-γ, IL-23, IL-17, IL-6, and IL-10 were measured by an enzyme-linked immunosorbent assay (ELISA). Results: Treatment with alfacalcidol raised 25(OH)D levels from a mean of 23.5 ± 5.6 to 34.5 ± 7.4 ng/mL (p = 0.059; NS). Alfacalcidol treatment decreased both Th1- (IL-12 and IFN-γ) and Th17-related (IL-23, IL-17, IL-6) cytokine levels in UCTD patients, while the soluble IL-10 level increased (IL-12: 156.7 ± 75.2 vs. 87.5 ± 42.1 pg/mL, p < 0.001; IFN-γ: 41.5 ± 12.0 vs. 21.7 ± 9.9 pg/mL, p < 0.001; IL-23: 385.2 ± 82.2 vs. 210.0 ± 69.3 pg/mL, p < 0.001; IL-17: 37.8 ± 9.6 vs. 17.8 ± 4.5 pg/mL, p 0.009; IL-6: 39.4 ± 11.3 vs. 23.5 ± 6.3 pg/mL, p < 0.001, IL-10: 8.4 ± 3.0 vs. 21.4 ± 9.7 pg/mL, p < 0.001). Alfacalcidol improved the Th17nTreg imbalance, as it inhibited the IL-17 expression of Th17 cells, and increased the number of nTregs. The alfacalcidol might increase the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. Conclusion: Our findings support the idea that vitamin D influences the Th17nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.

Original languageEnglish
Pages (from-to)490-497
Number of pages8
JournalScandinavian Journal of Rheumatology
Volume39
Issue number6
DOIs
Publication statusPublished - Nov 1 2010

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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