The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells

Summary

Background

Plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis by secreting interferon-α. Vitamin D3 analogues are widely used to treat psoriasis, and the representative analogue calcipotriol (CAL) uniquely downregulates the cytokine production and chemotactic activity of pDCs. However, the molecular mechanism of action of CAL is not well understood.

Aim

To investigate effects of CAL on the Toll-like receptor 9–myeloid differentiation primary response gene 88 (TLR9-MyD88) signalling pathway, which induces cytokine production, in murine pDCs.

Methods

pDCs were isolated from mouse spleen cells by negative selection or were generated from mouse bone-marrow cells, and were stimulated with CpG-oligodeoxynucleotide (ODN) with or without CAL for 24 h. mRNA expression of TLR9 and MyD88 was assessed by real-time PCR, and the amount of TLR9 was measured by western blotting.

Results

CAL suppressed the CpG-ODN-induced increased expression of MyD88 and TLR9 in pDCs.

Conclusions

CAL may downregulate pDCs by inhibiting TLR9-MyD88 signalling.