1,25‐dihydroxyvitamin D3 modulates Th17 polarization and interleukin‐22 expression by memory T cells from patients with early rheumatoid arthritis

• Published in: Arthritis and rheumatism 2010-01, Vol.62 (1), p.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: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - pharmacology; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Calcitriol - pharmacology; CD28 Antigens - immunology; CD3 Complex - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Polarity - drug effects; Cell Polarity - immunology; Cell Separation; Dexamethasone - pharmacology; Diseases of the osteoarticular system; Drug Combinations; Female; Flow Cytometry; Humans; Immunologic Memory; Inflammatory joint diseases; Interleukin-17 - metabolism; Interleukin-22; Interleukins - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Male; Medical sciences; Middle Aged; Young Adult
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.25043

Objective To examine the immunologic mechanism by which 1,25‐dihydroxyvitamin D3 (1,25[OH]2D3) 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)2D3, dexamethasone (DEX), and 1,25(OH)2D3 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)2D3 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)2D3 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)2D3, 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)2D3 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.