Role of CD146 in bronchial epithelial differentiation and repair: implications for severe asthma - 09/05/26

Asthma is a chronic respiratory disease affecting nearly 300 million people worldwide, with 2–10% suffering from severe asthma. Bronchial epithelium dysfunction plays a central role in asthma pathophysiology. CD ₁₄₆ , an adhesion molecule highly expressed in vascular cells, is also present in epithelial cells, although its functions in this context remain poorly understood. We previously reported that CD ₁₄₆ is expressed by the bronchial epithelium and mainly by the basal cells. This study aimed to investigate the role of CD ₁₄₆ in bronchial epithelium differentiation and repair, and its implication in severe asthma.

Bronchial epithelia from healthy controls (C) and severe asthma (SA) patients were reconstituted in vitro using air-liquid interface culture. Undifferentiated bronchial epithelial cells ( n = 10 C; 6 SA) and CD ₁₄₆₋ sorted cells ( n = 10 C; 5 SA) were followed during differentiation. In parallel, CD ₁₄₆ expression was further assessed in differentiated epithelia ( n = 30 C; 26 SA). Then, CD ₁₄₆ was silenced using lentiviral shRNA in undifferentiated bronchial epithelial cells and its effects were followed until obtention of a fully differentiated epithelium ( n = 2). Finally, to better understand the potential involvement of CD ₁₄₆ in repair process, CD ₁₄₆ expression kinetics were evaluated in a 14-day virus-induced exacerbation model ( n = 6 C; 6 SA).

Loss of CD ₁₄₆ impaired epithelial differentiation, as evidenced by poorly differentiated epithelia reconstituted from CD ₁₄₆₋ cells. In unsorted cultures, CD ₁₄₆ expression decreased during differentiation (−70% from day 0 to day 28, p < 0.05), while shRNA-mediated silencing seems to confirm its role in this process. In severe asthma, CD ₁₄₆ was significantly overexpressed at both mRNA (+219%, p < 0.0001) and protein (+34%, p < 0.05) levels in differentiated epithelium and differences in the differentiation has been observed. During a virus-induced exacerbation, CD ₁₄₆ seems to be involved in the epithelium repair.

Our findings identify CD ₁₄₆ as a key regulator of bronchial epithelial differentiation and repair. Its overexpression in severe asthma highlights a potential contribution to disease pathophysiology and suggests CD ₁₄₆ as a novel target for therapeutic investigation.