Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease.
Scand J Rheumatol
; 39(6): 490-7, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20615161
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+CD25â» 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiência de Vitamina D
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Linfócitos T Reguladores
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Doenças do Tecido Conjuntivo
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Conservadores da Densidade Óssea
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Células Th17
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Homeostase
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Hidroxicolecalciferóis
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article