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Understanding Psoriasis: how Vitamin D analogues reduce imiquimod-induced psoriasis-like lesions

Topical Vitamin D analogues alone have shown a beneficial effect in the treatment of psoriasis (calcipotriol,  calcitriol…)

Calcipotriol (MC903) slows down the rate of skin cell growth, flattens psoriasis lesions, and removes scales (More on MC903 after the conclusion). When looking more closely, it improves psoriasis by inhibiting proliferation and inducing terminal differentiation. This study seeks to investigate its immunomodulatory effect,

-The following article notes therapies which target Il-12 and Il-23 (Click HERE). Note that guselkumab (link) is specific to Il23 (phase 3) and it would be interesting (scientifically speaking) to show the efffect of this future treatment of psoriasis in the reduction of imiquimod-induced lesions in humans

-In this study from Kyoto, Japan, the authors applied MC903 on psoriasis skin of mice. The lesions were induced by imiquimod (IMQ) application as it is an agonist of Toll-Like receptors 7 and 8
It prevented the development of lesions clinically visible and on histology.

How does MC903 act in IMQ-induced psoriasiform lesions ?
-In psoriasis, there is upregulation of expression of inflammatory chemokines:  Il-17a, Il-22, Il-12 p40, Il-23a (p19) – this is almost completely suppressed by MC903
-The proportion of gamma-delta T-cells producing IL17 and Il22 is markedly reduced

Hypothesis
Il17 and Il22 production is promoted by Il-23 in IMQ-induced psoriasis lesions
MC903 could exert its effect by impairing expression of Il23: indeed mRNA of Il-23 (and Il-12 p40) upregulated is suppressed by MC903
At the same time it was found in vitro that the expression of Il-12 p40 and Il-23 RNA was suppressed by MC903 when were murine primary Langerhans Cells or human monocyte-derived Dendritic Cells.

Conclusion
The authors also show here that MC903 is effective in reducing imiquimod-induced psoriasis-like effects partly through inhibition of production of interleukin 23 (Il-23) which is a specific mediator of inflammation produced by macrophages (Langerhans cells)

 

 

More on Calcipotriol

About MC903 (calcipotriol)
-Calcipotriol carries the research name MC903, after Martin Calverey who first synthesized it. Contrarily to its precursor (1alpha25 (OH)2 D3), it had 100 times less action on calcium metabolism.

Where did the idea to use vitamin D analogues come from ?
Shigeto Morimoto, had described how one of his patients suffering from senile osteoporosis when treated orally with alfacalcidol showed a remarkable improvement in his lifelong psoriasis

It has been found that Vitamin D receptors are present in keratinocytes (1979). Calcipotriol also inhibitis fibroblast growth (1983), and induces keratinocyte differentiation (1985)

 

 

Source of information: P01-07 [C07-02] Kusuba et al. Vitamin D analogue MC903 improves imiquimod-induced psoriatic skin lesion via directly inhibiting IL-23 production by Langerhans cells. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2015 – Okayama, Japan
Bibliography: Maiddin WS. To Heal the Skin – The Heroes Behind Discoveries in Dermatology. 1st Edition 2015. Lincare Books