The vitamin D analog, maxacalcitol, reduces psoriasiform skin inflammation by inducing regulatory T cells and downregulating IL-23 and IL-17 production.

BACKGROUND

Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D analogs (VD3 As).

OBJECTIVE

To compare the effects of a VD3 A maxacalcitol and betamethasone valerate (BV) steroid lotion on topical imiquimod (IMQ)-induced psoriasiform skin inflammation.

METHODS

Female BALB/c mice were treated with vehicle, maxacalcitol or BV lotion on the skin for 3 days, and IMQ cream for 6 days. q-PCR, H&E, immunohistochemistry and immunofluorescence studies were performed on skin samples. Additionally, mice were treated with vehicle, maxacalcitol or BV lotion for 3 days and CD4CD25 regulatory T cells (Tregs) and CD4CD25 cells from each group were isolated from lymph nodes. Adoptive transfer of the cells was performed on recipient mice which were treated with IMQ cream for 6 days, and skin samples were obtained for q-PCR and H&E staining.

RESULTS

Maxacalcitol and BV were comparable in regards clinical improvement, although maxacalcitol reduced the MHC Class II inflammatory cell infiltration more than BV in IMQ skin. While both treatments downregulated IL-17 A, IL-17 F, IL-22, IL-12p40, TNF-α and IL-6 mRNA expression levels, only maxacalcitol downregulated IL-23p19 expression. Significantly increased Foxp3 cell infiltrations and IL-10 expression were noted in maxacalcitol-treated IMQ skin. Adoptive transfer of Treg cells from maxacalcitol-treated donor mice improved IMQ-induced inflammation clinically and histopathologically more than the recipients of Treg cells from BV-treated donor groups, showing reduced levels of inflammatory cytokines and increased IL-10 expression.

CONCLUSION

These results indicate that maxacalcitol reduces psoriasiform skin inflammation by inducing Treg cells as well as downregulating IL-23 and IL-17 production.