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Disrupting the IL-36 and IL-23/IL-17 loop underlies the efficacy of calcipotriol and corticosteroid therapy for psoriasis
Beatriz Germán, … , Katia Boniface, Mei Li
Beatriz Germán, … , Katia Boniface, Mei Li
Published January 24, 2019
Citation Information: JCI Insight. 2019;4(2):e123390. https://doi.org/10.1172/jci.insight.123390.
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Categories: Research Article Dermatology Inflammation

Disrupting the IL-36 and IL-23/IL-17 loop underlies the efficacy of calcipotriol and corticosteroid therapy for psoriasis

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Abstract

Psoriasis is one of the most common skin inflammatory diseases worldwide. The vitamin D3 analog calcipotriol has been used alone or in combination with corticosteroids in treating plaque psoriasis, but how it suppresses psoriatic inflammation has not been fully understood. Using an experimental mouse psoriasis model, we show that topical calcipotriol inhibited the pivotal IL-23/IL-17 axis and neutrophil infiltration in psoriatic skin, and interestingly, such effects were mediated through the vitamin D receptor (VDR) in keratinocytes (KCs). We further reveal that IL-36α and IL-36γ, which have recently emerged as key players in psoriasis pathogenesis, were effectively repressed by calcipotriol via direct VDR signaling in mouse KCs. Accordingly, calcipotriol treatment suppressed IL-36α/γ expression in lesional skin from patients with plaque psoriasis, which was accompanied by a reduced IL-23/IL-17 expression. In contrast, dexamethasone indirectly reduced IL-36α/γ expression in mouse psoriatic skin through immune cells. Furthermore, we demonstrate that calcipotriol and dexamethasone, in combination, synergistically suppressed the expression of IL-36α/γ, IL-23, and IL-17 in the established mouse psoriasis. Our findings indicate that the combination of calcipotriol and corticosteroid efficiently disrupts the IL-36 and IL-23/IL-17 positive feedback loop, thus revealing a mechanism underlying the superior efficacy of calcipotriol and corticosteroid combination therapy for psoriasis.

Authors

Beatriz Germán, Ruicheng Wei, Pierre Hener, Christina Martins, Tao Ye, Cornelia Gottwick, Jianying Yang, Julien Seneschal, Katia Boniface, Mei Li

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Figure 4

Topical treatment of calcipotriol downregulates hIL-36α and hIL-36γ expression in human psoriasis skin.

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Topical treatment of calcipotriol downregulates hIL-36α and hIL-36γ expr...
Skin biopsies were taken from healthy donors (HD), or from lesional skin of plaque psoriatic patients (PP) before and after a 4-day topical treatment with Calcipotriol ointment (DAIVONEX) once a day, and qPCR analyses were performed. Individual values are shown, with the line connecting paired samples from the same patient before and after the calcipotriol treatment.
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