Targeting the Semaphorin3E-plexinD1 complex in allergic asthma

Asthma is a heterogenous airway disease characterized by airway inflammation and remodeling. It affects more than 300 million people worldwide and poses a significant burden on society. Semaphorins, discovered initially as neural guidance molecules, are ubiquitously expressed in various organs and regulate multiple signaling pathways. Interestingly, Semaphorin3E is a critical molecule in lung pathophysiology through its role in both lung development and homeostasis. Semaphorin3E binds to plexinD1, mediating regulatory effects on cell migration, proliferation, and angiogenesis. Recent in vitro and in vivo studies have demonstrated that the Semaphorin3E-plexinD1 axis is implicated in asthma, impacting inflammatory and structural cells associated with airway inflammation, tissue remodeling, and airway hyperresponsiveness. This review details the Semaphorin3E-plexinD1 axis in various aspects of asthma and highlights future directions in research including its potential role as a therapeutic target in airway allergic diseases.