Combined Maxacalcitol/Betamethasone Butyrate Propionate Ointment Possesses Long-Term Sustained Effects - Inducing Regulatory T Cells and Downregulating the Th17 Response

Sep 30, 2026

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We often experience sustained improvement after stopping psoriasis treatment using topical vitamin D3 (VD3) or combined topical corticosteroids and VD3, yet the mechanisms are unclear. This study investigated sustained effects of maxacalcitol (MCT) and combined MCT/betamethasone butyrate propionate (BBP) using an imiquimod (IMQ)-induced murine psoriasiform model. Ointments were given before IMQ, then IMQ was reapplied 1–3 weeks later. MCT and MCT/BBP improved lesions and reduced Th17-related cytokines via IL-10 induction and Foxp3+ regulatory T cells, persisting longer with MCT/BBP.

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CategoryHealthcare

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Reading Time25 min

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Abstract

Introduction

The Journal of Dermatology ORIGINAL ARTICLE OPEN ACCESS Combined Maxacalcitol/Betamethasone Butyrate Propionate Ointment Possesses Long-Term Sustained Effects of Inducing Regulatory T Cells and Downregulating the Th17 Response, Even After Discontinuation of Its Application in Imiquimod-Induced Psoriasiform Dermatitis Teruo Shimizu1 | Masahiro Kamata1 | Hideya Uratsuji2 | Yoshiki Okada1 | Ayu Watanabe1 | Azusa Hiura1 | Yayoi Tomura1 | Yayoi Tada1 1Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan | 2Maruho Co. , Ltd. , Osaka, Japan Correspondence: Masahiro Kamata ([mkamata-tky@umin.ac.jp](mkamata-tky@umin.ac.jp)) Received: 14 March 2025 | Revised: 23 September 2025 | Accepted: 15 October 2025 Funding: This work was supported by Maruho Co. , Ltd. Keywords: betamethasone butyrate propionate | interleukin-10 | interleukin-17 | maxacalcitol | psoriasis | regulatory T cells ABSTRACT We often experience sustained improvement, even after discontinuation of treatment in psoriasis lesions treated with topical vitamin D3 (VD3) or the combination of topical corticosteroids andVD3. However, the underlying mechanisms of these sustained effects remain unclear. We explored mechanisms for the sustained effects of maxacalcitol (MCT) and combined MCT/betamethasone butyrate propionate (BBP) ointments using a murine psoriasiform dermatitis model induced by imiquimod (IMQ) . IMQ was applied once daily to the shaved backs of mice for 6 days to induce psoriasiform dermatitis. MCT, BBP, combined MCT/BBPointment, or their vehicles were treated for 3 days prior to IMQ application. IMQ was reapplied after 1, 2, or 3 weeks from the first IMQ application to investigate the sustained effects of their ointments. In the first application of IMQ, the administration of MCT, BBP, or MCT/BBP ointment improved clinical and pathological manifestations and reduced Th17-related cytokines. Treatment with MCT or MCT/BBP showed an increase in IL-10 mRNA expression and a higher count of Foxp3+ cells within the skin, but not in those with BBP. The induction of IL-10 by MCT and MCT/BBP persisted until reapplication of IMQ 2 weeks later, although their effects diminished 3 weeks later. The reduction in Th17-related cytokines was maintained up to 3 weeks later in MCT/BBP, whereas it was not observed 2 weeks later in MCT. In conclusion, MCT and MCT/BBP showed long-term effects by induction of regulatory T cells and IL-10. Additionally, MCT/BBP downregulated Th17-related cytokines, which could contribute to the sustained improvement after discontinuation observed in clinical practice. 1 | Introduction Psoriasis is a chronic skin disorder characterized by erythematous and scaly plaques. Recently, it has been considered a systemic inflammatory disease associated with arthritis and metabolic syndrome. The etiology of this disease reportedly includes genetic factors; immunological abnormalities including Th1/Th17, dendritic cells, neutrophils, macrophages, and | Abbreviations: BBP, betamethasone butyrate propionate; IL, interleukin; IMQ, imiquimod; LN, lymph node; MCT, maxacalcitol; PCR, polymerase chain reaction; Tregs, regulatory T cells; VD3, vitamin D3. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2025 The Author(s) . The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association. | The Journal of Dermatology, 2026; 53:25–34 25 [https://doi.org/10.1111/1346-8138.70031](https://doi.org/10.1111/1346-8138.70031) B cells; and abnormal differentiation and proliferation of keratinocytes [1–5] . The interleukin (IL)-17/IL-23 cytokine pathway plays a significant role in the pathogenesis of the disease since the biologics targeting these cytokines are highly effective [6–8] . As an animal psori

FAQs

What was the main goal of investigating MCT and MCT/BBP ointments?

To clarify the mechanisms behind long-term sustained improvement in psoriasis lesions after discontinuing topical treatment, focusing on regulatory T cells and Th17 responses.

How was the psoriasiform dermatitis model induced and used to test sustained effects?

Mice received daily IMQ on shaved backs for 6 days, with ointments administered for 3 days before IMQ; IMQ was then reapplied 1, 2, or 3 weeks later to assess persistence after discontinuation.

What immune changes were associated with the sustained effects?

MCT and MCT/BBP increased IL-10 expression and Foxp3+ regulatory T cells in skin, and reduced Th17-related cytokines; IL-10 induction persisted longer than some Th17-related effects depending on the reapplication timing.

Sep 30, 2026

Uploaded by Fahsai