Involvement of epithelial CD146 in severe asthma

Abstract

Introduction

Asthma is a chronic lung disease affecting 300 million people worldwide, 2-10 % of whom suffer from severe asthma. In asthma, the bronchial epithelium is dysregulated, contributing to the pathophysiology of the disease. CD₁₄₆ is an adhesion molecule that is highly expressed on all the cells from the vascular system, including endothelial cells. It is also expressed by epithelial cells, but its functions in these cells are poorly understood, as is its role in severe asthma. The aim of our study is to elucidate the role of CD₁₄₆ in the bronchial epithelium and its implication in severe asthma.

Methods

Bronchial epithelia of healthy controls and severe asthma patients were reconstituted in vitro using air-liquid interface culture. Measurements of CD₁₄₆ expression were made on differentiated epithelium (n = 20 control and 20 severe asthma patients). Then, undifferentiated and differentiated bronchial epithelial cells were sorted based on the expression level of CD₁₄₆. The sorted undifferentiated bronchial epithelial cells were cultured and monitored during the differentiation process until obtention of a fully differentiated epithelium (n = 3). The sorted differentiated bronchial epithelial cells were used to perform RNA-Seq experiments (n = 4).

Results

We showed that CD₁₄₆ is highly expressed in severe asthma patients compared to healthy controls both at mRNA and protein levels in differentiated epithelium. Then, we have shown that CD₁₄₆ expression is not ubiquitous in the differentiated bronchial epithelium. Cell sorting and RNA-seq experiments demonstrated that CD₁₄₆ is mostly expressed by the basal epithelial cells in the differentiated epithelium. Finally, morphological analysis revealed that CD₁₄₆ seems to play a role in the bronchial epithelium differentiation process. Indeed, fully differentiated epithelium obtained from CD₁₄₆+ and CD₁₄₆− sorted undifferentiated bronchial epithelial cells were different in morphology and cell composition.

Conclusion

Our results suggest that CD₁₄₆ is only expressed by basal cells of the bronchial epithelium and supports an important role in the differentiation of this epithelium. Moreover, we demonstrated that CD₁₄₆is overexpressed in severe asthma, suggesting a possible role of this molecule in this disease notably during repair epithelial process.