Protocadherin-1: epithelial barrier dysfunction in asthma and eczema

Abstract

Asthma and eczema result from the interaction between genetic susceptibility and environmental exposures. Over the last two decades, genetic studies have led to the identification of multiple susceptibility genes, increasing our understanding of the biological pathways leading to these diseases. Many asthma and eczema susceptibility genes are expressed in epithelial cells of airway mucosa and skin [1]. The epithelium constitutes the first line of defence against allergens and invading microbes. Recently, loss of epithelial integrity has been implicated as an important mechanism leading to both asthma [2] and eczema [3]. In this issue of the European Respiratory Journal , Mortensen et al. [4] report the association of genetic variants in the gene encoding protocadherin-1 ( PCDH1 ) with asthma, wheeze and eczema in (early) childhood in the Danish birth cohort study COPSAC (Copenhagen Studies on Asthma in Childhood). Their studies also suggest a gene–environment interaction of PCDH1 with passive smoke exposure in early childhood in asthma development. These studies expand on previous data reporting a role for PCDH1 polymorphisms in the susceptibility to both asthma [4–7] and eczema [4, 6, 8]. Given the replicated association of PCDH1 with both diseases, this gene might contribute to a biological pathway that constitutes a shared cause for both diseases. Here, we will summarise the cumulative data on PCDH1 polymorphisms in asthma and eczema, and make an attempt to interpret these genetic data in light of PCDH1 expression and function as a contributor to epithelial integrity. In 1993, PCDH1 was originally identified by Sano et al. [9] as protocadherin-42 and was reported to induce cell adhesion upon ectopic membrane expression in a mouse fibroblast L-cell assay. PCDH1 is a member of the δ1 subfamily of the …