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

Abstract

OBJECTIVE:

The aim of this study was to perform a quantitative and functional analysis of natural CD4+CD25(high)Foxp3+ 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 Th17/nTreg 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 Th17/nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.

• Authors: E Zold, P Szodoray, J Kappelmayer, J Gaal, L Csathy, S Barath, E Gyimesi, A Hajas, M Zeher, G Szegedi, E Bodolay
• Journal: Scandinavian journal of rheumatology (Scand J Rheumatol) Vol. 39 Issue 6 Pg. 490-7 (Nov 2010) ISSN: 1502-7732 [Electronic] England
• PMID: 20615161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Bone Density Conservation Agents
• Cytokines
• FOXP3 protein, human
• Forkhead Transcription Factors
• Hydroxycholecalciferols
• Interleukin-17
• Vitamin D
• alfacalcidol

Topics

• Adult
• Autoantibodies (blood)
• Bone Density Conservation Agents (adverse effects, therapeutic use)
• Connective Tissue Diseases (immunology)
• Cytokines (blood, metabolism)
• Female
• Forkhead Transcription Factors (blood, metabolism)
• Homeostasis (drug effects, immunology)
• Humans
• Hydroxycholecalciferols (adverse effects, therapeutic use)
• Interleukin-17 (blood, metabolism)
• Middle Aged
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Th17 Cells (drug effects, immunology)
• Vitamin D (blood, metabolism)
• Vitamin D Deficiency (drug therapy, immunology)
• Young Adult