Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

Abstract

Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2-3% of the world's population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.

Keywords: CYP11A; RORα; RORγ; VDR; megalin; psoriasis; vitamin D.

Figure 1

The major effector cells and signaling pathways in the immunopathogenesis of psoriasis.

Figure 2

Immunostaining of VDR, RORα and RORγ, and LRP2/megalin in psoriasis and normal skin. Histology of lesional skin shows skin with regular psoriasiform epidermal hyperplasia, prominent dilated vessels with an edematous dermal papillae, mounds of parakeratosis containing neutrophils, and a superficial perivascular lymphocytic infiltrate. Scale bars = 100 μm.