1,25‐dihydroxyvitamin D 3 modulates Th17 polarization and interleukin‐22 expression by memory T cells from patients with early rheumatoid arthritis

• Published in: Arthritis and rheumatism Vol. 62; no. 1; pp. 132 - 142
• Main Authors: Colin, E. M., Asmawidjaja, P. S., van Hamburg, J. P., Mus, A. M. C., van Driel, M., Hazes, J. M. W., van Leeuwen, J. P. T. M., Lubberts, E.
• Format: Journal Article
• Language: English
• Published: 01-01-2010
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.25043

Abstract
Objective
To examine the immunologic mechanism by which 1,25‐dihydroxyvitamin D
3
(1,25[OH]
2
D
3
) may prevent corticosteroid‐induced osteoporosis in patients with early rheumatoid arthritis (RA), with a focus on T cell biology.
Methods
Peripheral blood mononuclear cells (PBMCs) and CD4+CD45RO+ (memory) and CD4+CD45RO− (non‐memory) T cells separated by fluorescence‐activated cell sorting (FACS) from treatment‐naive patients with early RA were stimulated with anti‐CD3/anti‐CD28 in the absence or presence of various concentrations of 1,25(OH)
2
D
3
, dexamethasone (DEX), and 1,25(OH)
2
D
3
and DEX combined. Levels of T cell cytokines were determined by enzyme‐linked immunosorbent assay and flow cytometry.
Results
The presence of 1,25(OH)
2
D
3
reduced interleukin‐17A (IL‐17A) and interferon‐γ levels and increased IL‐4 levels in stimulated PBMCs from treatment‐naive patients with early RA. In addition, 1,25(OH)
2
D
3
had favorable effects on tumor necrosis factor α (TNFα):IL‐4 and IL‐17A:IL‐4 ratios and prevented the unfavorable effects of DEX on these ratios. Enhanced percentages of IL‐17A– and IL‐22–expressing CD4+ T cells and IL‐17A–expressing memory T cells were observed in PBMCs from treatment‐naive patients with early RA as compared with healthy controls. Of note, we found no difference in the percentage of CD45RO+ and CD45RO− cells between these 2 groups. Interestingly, 1,25(OH)
2
D
3
, in contrast to DEX, directly modulated human Th17 polarization, accompanied by suppression of IL‐17A, IL‐17F, TNFα, and IL‐22 production by memory T cells sorted by FACS from patients with early RA.
Conclusion
These data indicate that 1,25(OH)
2
D
3
may contribute its bone‐sparing effects in RA patients taking corticosteroids by the modulation of Th17 polarization, inhibition of Th17 cytokines, and stimulation of IL‐4.