The vitamin D3 analog, maxacalcitol, reduces psoriasiform skin inflammation by inducing regulatory T cells and downregulating IL-23 and IL-17 production

Publication date: Available online 24 August 2018

Source: Journal of Dermatological Science

Author(s): Carren S. Hau, Teruo Shimizu, Yayoi Tada, Masahiro Kamata, Shintaro Takeoka, Sayaka Shibata, Aya Mitsui, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Shinichi Sato, Shinichi Watanabe

Abstract

Background

Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D₃ 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 CD4⁺CD25⁺ regulatory T cells (Tregs) and CD4⁺CD25- 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.

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