Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin

Malin Assarsson,Albert Duvetorp,Jan Söderman,Marita Skarstedt,Ulrich Mrowietz,Oliver Seifert

doi:10.1007/s00403-019-01931-y

Abstract

WNT/β-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohn’s disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

Highlights

WNT proteins are a family of secreted glycoproteins with 19 isoforms
The aim of this study was to describe the expression of WNT7B, WNT10B, WNT16 and transcription factor 7-like 2 (TCF7L2) in lesional and non-lesional skin and in whole blood of patients with psoriasis compared to healthy individuals and to investigate if single nucleotide polymorphisms (SNPs) in these genes can be correlated to psoriasis
Gene expression analysis revealed significantly decreased WNT7B, WNT10B and TCF7L2 expression levels in lesional skin compared to non-lesional skin of patients with psoriasis (p < 0.001) (Fig. 2a–c)

Summary

Introduction

WNT proteins are a family of secreted glycoproteins with 19 isoforms. Recent reports suggest a role of WNTs in inflammation, psoriasis and the human immune defense against infections [6, 22, 23, 37, 40, 42]. WNTs can activate two distinct signaling pathways: the canonical WNT/β-catenin pathway and the β-catenin-independent, non-canonical pathway [9]. Psoriasis is a chronic systemic inflammatory disease characterized by activation of both innate and adaptive immunity [34]. Dendritic cells play a key role in linking innate and adaptive immunity and in balancing inflammatory and regulatory responses. A recent study showed that activation of WNT/β-catenin signaling in dendritic cells is critical for promoting tolerance and limiting inflammation [45]

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