1,25-Dihydroxyvitamin D-3 Modulates Th17 Polarization and Interleukin-22 Expression by Memory T Cells From Patients With Early Rheumatoid Arthritis

E. M. Colin*, P. S. Asmawidjaja, J. P. van Hamburg, A. M. C. Mus, M. van Driel, J. M. W. Hazes, J. P. T. M. van Leeuwen, E. Lubberts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

238 Citations (Scopus)

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-gamma 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 alpha (TNF alpha):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, TNF alpha, 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.
Original languageEnglish
Pages (from-to)132-142
Number of pages11
JournalArthritis & Rheumatism
Volume62
Issue number1
DOIs
Publication statusPublished - Jan 2010

Research programs

  • EMC MM-01-39-02
  • EMC MM-02-72-02
  • EMC MUSC-01-31-01

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