IL-4/IL-13 pathway in nasal type 2 inflammation: The central role and targeted therapy

Type 2 dominant inflammation in nasal mucosa is the key underlying pathophysiological mechanism of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin-4 (IL-4) and IL-13 share common receptor subunits and signaling molecules, which lead to various pathological changes in different cells, playing key roles in the pathogenesis of nasal type 2 inflammation. Numerous clinical trials have shown that biologics targeting key molecules of the IL-4/IL-13 pathway, especially IL-4 receptor alpha, can treat CRSwNP and AR with high efficacy, and are generally well tolerated. Several biologics have been approved for the treatment of difficult-to-control CRSwNP, while others also show promising results. Here, we review the IL-4/IL-13 pathway, its role in nasal type 2 inflammation, and current targeted therapies related to the IL-4/IL-13 pathway, with a focus on AR and CRSwNP.